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People are inundated with popular press reports about medical research concerning what's healthy, get advice from doctors, and hear personal anecdotes. How do people integrate conflicting anecdotal and statistical information when making medical decisions? In four experiments (N = 4,125), we tested how people integrate conflicting information to judge the efficacy of artificial and real medical treatments. Participants read an anecdote from someone in a clinical trial, or who had undergone a medical treatment previously, for whom the medical treatment was ineffective. We found that reading anecdotes for either artificial or real medical treatments shifted participants' beliefs about the efficacy of a medical treatment. We observed this result even when the anecdote was uninformative, was paired with an icon array, or when participants were provided with thorough medical decision-aids about reproductive health procedures. Our findings highlight the pervasive effect of anecdotes on medical decision-making.

Cardiolipin is one of the main phospholipid components of Staphylococcus aureus membranes. This lipid is found at varying concentrations in the bilayer, depending on the growth stage of the bacteria, and as a response to environmental stress. Cardiolipin is an anionic phospholipid with four acyl chains, which modulates the bending properties of the membrane due to its inverted conical shape. It has been shown to inhibit the pore forming activity of several antimicrobial peptides, in general doubling the peptide concentration needed to induce leakage. Here we find that the short snake-derived antimicrobial peptide ATRA-1 is inhibited by several orders of magnitude in the presence of cardiolipin in saturated membranes (DMPG) compared to the human cathelicidin LL-37, which is only inhibited two-fold in its leakage-inducing concentration. The ATRA-1 is too short to span the membrane and its leakage activity is likely related to detergent-like alterations of bilayer structure. Fluorescence spectroscopy shows only a minor effect on ATRA-1 binding to DMPG membranes due to the presence of cardiolipin. However, FTIR spectroscopy shows that the acyl chain structure of DMPG membranes, containing cardiolipin, become more organized in the presence of ATRA-1, as reflected by an increase in the gel to liquid-crystalline phase transition temperature. Instead, a depression in the melting temperature is induced by ATRA-1 in DMPG in the absence of cardiolipin. In comparison, LL-37 induces a depression of the main phase transition of DMPG even in the presence of cardiolipin. These data suggest that cardiolipin inhibits the penetration of ATRA-1 into the membrane core, impeding its capacity to disrupt lipid packing.

13 Páginas.-- 5 Figuras.--3 Tablas, Obesity is associated with disruptions in the adaptive immune system; however, dietary fatty acids in high-fat diets (HFDs) that induce obesity have consequences that are currently unclear regarding T-cell maintenance in bone marrow (BM). C57BL/6J mice were randomly assigned to isocaloric HFDs formulated with dietary fats rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), or MUFAs supplemented with eicosapentaenoic and docosahexaenoic acids for 20 weeks, followed by an analysis of the immunophenotypic feature of lymphocytes (CD3+) T and their subsets CD4+ and CD8+ T cells in spleen and BM, identification of fatty acids in BM extracellular fluid and analysis of the correspondence between fatty acids with the frequency of T-cell subsets in BM. Splenic CD3+ T cells were reduced irrespective of HFDs. In BM, CD3+ T cells were reduced after HFD-SFAs, while CD4+ T cells were increased after HFDs enriched in MUFAs and CD8+ T cells were reduced irrespective of HFDs. In BM extracellular fluid, the content of palmitic and myristic acids increased after HFD-SFAs and that of oleic acid increased after HFDs enriched in MUFAs. There was a statistical correspondence between HFD-induced changes in fatty acids in BM extracellular fluid and HFD-induced changes in the frequency of CD3+ and CD4+ T cells in BM. These findings reveal an undervalued critical role for dietary fatty acids in the selective acquisition of T-cell subsets in BM, highlighting that oleic acid existing in the surroundings of T-cell niches during HFD-induced obesity could be instrumental in the maintenance of CD4+ T cells., This work was supported by a grant AGL2016-80852-R funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe.”

Obesity is associated with disruptions in the adaptive immune system; however, dietary fatty acids in high-fat diets (HFDs) that induce obesity have consequences that are currently unclear regarding T-cell maintenance in bone marrow (BM). C57BL/6J mice were randomly assigned to isocaloric HFDs formulated with dietary fats rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), or MUFAs supplemented with eicosapentaenoic and docosahexaenoic acids for 20 weeks, followed by an analysis of the immunophenotypic feature of lymphocytes (CD3

19 Páginas.-- 5 Figuras.-- 5 Tablas, The phytochemical composition of leaves, stems, pericarps and rhizomes ethanolic extracts of Asparagus acutifolius were characterized by HPLC-DAD-MS. A. acutifolius samples contain at least eleven simple phenolics, one flavonon, two flavonols and six steroidal saponins. The stem extracts showed the highest total phenolic acid and flavonoid contents, where cafeic acid and rutin were the main compounds. No flavonoids were detected in the leaf, pericarp or rhizome while caffeic acid and ferulic acid were the predominant. Steroidal saponins were detected in the different plant parts of A. acutifolius, and the highest contents were found in the rhizome extracts. The stem extracts exhibited the highest antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) and the highest 2,2-azino-bis (3 ethylbenzothiazoline-6-sulphonic acid) (ABTS) scavenging activity was found in the pericarp extracts. The rhizome and leaf extracts showed a potent cytotoxic activity against HCT-116 and HepG2 cell lines. Moreover, the pericarp and rhizome extracts revealed a moderate lipase inhibitory activity. The leaf and rhizome extracts were screened for their antimicrobial activity against human pathogenic isolates. The leaf extract exhibited a powerful inhibitory activity against all the bacteria and fungi tested., This research was funded by the Tunisian Ministry of Scientific Research and Technology and by the Ministerio de Ciencia e Innovación of Spain (AGL2017-82428-R).

Our aim was to assess the combination of olive tree-related extracts with the most favorable profile of in vitro bioactive properties. We tested the antioxidant (increment of low-density lipoprotein resistance against oxidation), vasoactive (promotion of nitric oxide release and decrease of endothelin-1 production in human umbilical vein endothelial cells), anti-inflammatory (decrease of the endothelial production of vascular cell adhesion molecule-1), and antithrombotic (reduction of the endothelial release of plasminogen activator inhibitor-1) capacities of six phenolic extracts and three triterpenic acid solutions (Ps and Ts, respectively). We tested extracts alone and in combination, at nutritional (Ps: 0.05–0.5 mol/L; Ts: 0.001–0.1 mol/L) and nutraceutical doses (Ps: 1–10 mol/L; Ts: 0.25–10 mol/L). The combination of Ps rich in 3,4-dihydroxyphenylglycol (76%, P2), hydroxytyrosol (95%, P3), and oleuropein (70%, P4) (final nutritional concentration: 0.15 mol/L; final nutraceutical concentration: 3 mol/L) was the best in order to prepare functional products and nutraceuticals with cardioprotective properties, despite the fact that the isolated extract with the greatest in vitro properties was P5 (75% oleocanthal), suggesting a potential synergistic effect among different olive components., Spanish Ministry of Economy, Industry and Competitiveness, through the FEDER INNTERCONECTA Program of the Center for Industrial Technological Development (CDTI), Junta de Andalucía ITC-20151142 EXP 00083147, Instituto de Salud Carlos III European Commission CB06/03/0028 CD17/00122 CES12/025 JR17/00022, European Commission

11 Páginas.-- 6 Figuras.-- 3 Tablas, In Algeria, Fraxinus angustifolia Vahl (Oleaceae) is a prominent ingredient for the treatment of inflammatory diseases caused by oxidative stress. This study aimed to make a comparison between the phenolic compound compositions of the ethanolic and aqueous extracts (decoction and infusion) of this plant and to test the antioxidant, cytotoxic and anti-pancreatic lipase activities of the ethanolic extracts from the leaf and bark. The identification and quantification of phenolic compounds was carried out by HPLC-DAD-MS and the antioxidant activity was assessed according to three methods: Ferric Reducing Antioxidant Power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging activity and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity. The cytotoxic effect was investigated using the human colon adenocarcinoma cell line HCT-116; while pancreatic lipase inhibitory activity was examined using 4-nitrophenyl butyrate (NPB) as a substrate. A large variety of phenolic compounds were detected and the content of the leaf was much higher than that of the bark. The ethanolic extracts from the leaf had a higher antioxidant capacity than those of the bark, however, the latter showed greater antilipase activity and cytotoxicity than the former. These results suggest that this plant may be an important source of active compounds with a variety of biological activities which justify its use in traditional medicine., This work was supported by the Spanish Ministry of Science and Innovation (AGL2017-82428-R).

The aim of this work was to study the saponin profiles from spears of different wild asparagus species in the context of its genetic diversity aside from geographical seed origin. They included Asparagus pseudoscaber Grecescu, Asparagus maritimus (L.) Mill., Asparagus brachiphyllus Turcz., Asparagus prostrates Dumort., and Asparagus officinalis L. The saponin analysis by LC-MS has shown that saponin profile from wild asparagus is similar to that previously described for triguero asparagus from Huetor-Tajar landrace (triguero HT), which had not ever been reported in the edible part of asparagus. All the samples, except A. officinalis, were characterized for having saponins distinct to protodioscin and the total saponin contents were 10-fold higher than those described for commercial hybrids of green asparagus. In particular, A. maritimus from different origins were rich in saponins previously found in triguero HT. These findings supported previous suggestion, based on genetic analysis, about A. maritimus being the origin of triguero HT. Multivariate statistics including principal component analysis and hierarchical clustering analysis were used to define both similarities and differences among samples. The results showed that the greatest variance of the tested wild asparagus could be attributed to differences in the concentration of particular saponins and this knowledge could be a tool for identifying similar species.

33 Páginas; 5 Tablas; 4 Figuras, Asparagus by-products were submitted to hydrothermal treatments to improve their solubility and antioxidant capacity. Four severity conditions were applied (logRo 3.05, 3.64, 4.23, 4.82) and two fractions were isolated from each treatment. The solid fibrous residues were enriched in cellulose, and depleted of hemicelluloses and phenolics. Their antioxidant activities were higher than those presented for asparagus bioactive fibers (81–154 vs 21–26 mmol Trolox/Kg) and did not correlate with phenol content. The soluble liquors were rich in phenolics and also contained changeable amounts of mono-, oligo-, and polysaccharides as a function of severity. The majority of the released oligosaccharides (xylooligosaccharides) are considered as prebiotic and their percentage could be optimized by modifying hydrothermal treatment conditions. This fraction presented very high antioxidant activity (131–232 mmol Trolox/Kg), and had a moderate correlation with phenols. Melanoidins are suggested to be present in both fractions. A new fiber fraction with potential prebiotic activity and high antioxidant activity has been obtained from asparagus by-products. Its high solubility in water and a pleasant flavor broaden its applications in food formulations., This research was supported by the project AGL2017-82428-R from MINECO, Spanish Government.

Asparagus cultivation and consumption are widely spread throughout the world. Several investigations about fresh asparagus have evidenced that they are a nutritionally well-balanced and one of the best sources of antioxidants being the green spears richer than the white ones. However, there is scarce information on quality of canned asparagus. In the present work, we have studied chemical and phytochemical composition of 21 distinct presentations of asparagus, representative of the distinct brands available in Spanish markets. Our results revealed that this appreciated product continued to be of high nutritional quality after industrial processing, containing 1-1.8% bioactive fiber and 1-3% proteins. In addition, it contained significant quantities of several bioactive compounds, mainly ascorbic acid (6-12 mg/100g) and phenolics that in green asparagus ranged 16-46 mg/100g. Asparagus variety seems to be the factor that most influence the composition and quality of the final product. There were two samples of green asparagus that stand out from all others and that correspond to triguero asparagus from southern Spain. It can be concluded that the selection of varieties taking into account not only agronomic factors, but also phytochemical profile is determinant to obtain a product of the highest quality for both fresh and processed commercialization., This work was supported by the the Ministerio de Ciencia e Innovación of Spain (AGL2011-29632).

3 Figuras.-- 1 Tabla, Colorectal cancer is the third most common cancer in the world. Many efforts have focused on finding natural molecules with potential chemo-preventive activity due to their low toxicity compared to synthetic drugs. However, comprehensive information on the bioactive fractions and components is still missing. In this study, we developed a method for the quantitative separation and isolation of saponins from asparagus genotypes consisting of an adsorption chromatography and subsequent liquid chromatographic separation on a reversed-phase column. The saponins isolated were tested for their cytotoxic activity against human colon cancer cell lines, which could develop cross-resistance to a wide variety of chemotherapeutic drugs. Our results showed that Huétor-Tájar asparagus saponins (HTSAP), mainly protodioscin and HTSAP-10 have higher cytotoxic activity than HTSAP-1, HTSAP-6, and HTSAP-8. This study links the potential anticancer effect of asparagus to specific saponins and unveils the triguero Huétor-Tájar asparagus as a nutraceutical particularly in colon cancer therapies., Sergio López acknowledges the financial support from the Spanish MINECO (JCI‐2012‐13084, Juan de la Cierva, MINECO) and the ‘V Own Research Plan’ of the University of Seville (VPPI‐US) for his research contracts. These contracts are cofunded by the European Social Fund.

22 Páginas; 6 Figuras, Tyrosol (Tyr) is a phenolic compound found in virgin olive oil. After ingestion, Tyr undergoes extensive first pass intestinal/hepatic metabolism. However, knowledge about the biological effects of Tyr metabolites is scarce. We chemically synthesized Tyr glucuronate (Tyr-GLU) and sulphate (Tyr-SUL) metabolites and explored their properties against oxidative stress and inflammation in TNF-α-treated human umbilical vein endothelial cells (hECs). Tyr and Tyr-SUL prevented the rise of reactive oxygen species, the depletion of glutathione, and the down-regulation of glutathione peroxidase 1, glutamate-cysteine ligase catalytic subunit, and heme oxygenase-1 genes. Tyr-SUL and to a lower extent Tyr and Tyr-GLU prevented the phosphorylation of NF-κB signaling proteins. Tyr-GLU and Tyr-SUL also prevented the over-expression of adhesion molecules at gene, protein, and secretory levels, and the adhesion (Tyr-SUL > Tyr-GLU) of human monocytes to hECs. In vivo, Tyr, and most notably Tyr-SUL in a dose-dependent manner, ameliorated plantar and ear edemas in mice models of acute and chronic inflammation. This study demonstrates the antioxidant and/or anti-inflammatory properties of Tyr metabolites, with Tyr-SUL being the most effective., We thank Angela Palma Pacheco for technical assistance. This study and the contracts of RL and APP were supported by the research Grant of the Junta de Andalucia, Spain (P09-CVI-5007). SM had the benefit of a FPI fellowship of the MICINN (BES-2012-056104) and BB of the “V Own Research Plan” of the University of Seville. SL had Juan de la Cierva contract cofunded by the European Social Fund (ESF) from the Spanish MINECO (JCI-2012-13084,) and the Spanish Research Council/JAEdoc Program (JAEDOC089).

5 Tablas.-- 3 Figuras, The ethanolic extracts from the leaves, pericarps and rhizomes of Asparagus albus L. were investigated for their phytochemical composition, antioxidant (DPPH and FRAP assays), anti-microbial against human pathogenic isolates and cytotoxic (human colon carcinoma HCT-116 cells) activities. The highest flavonoid content was obtained in the leaf extract followed by the pericarp but there were no flavonoids detected in the rhizome. However, the rhizome had a high concentration of saponins. Flavonoid and saponin profiles were similar to those previously described for the triguero Huetor Tajar asparagus landrace. It was found that the pericarp ethanolic extract exhibited higher antioxidant activity than rhizome and leaf extracts. Moreover, the rhizome possessed more evident cytotoxic activity against HCT-116 cells in comparison to leaf and pericarp. All extracts showed varying degrees of antimicrobial activity against most of the human pathogenic isolates. In addition, the leaves showed more powerful inhibitory activities against the maximum number of bacteria and all the fungai isolated and the highest activity was in the pericarp extract against multidrug resistant Pseudomonas aeruginosa (MDR) and Erythromycin resistant Streptococcus agalactiae (ER) with an inhibition zone of 21 mm and 19 mm, respectively. The results show that A. albus could be a new crop with pharmaceutical interest because its richness in bioactive compounds provides considerable benefits for human health., This work was supported by the Tunisian Ministry of Scientific Research and Technology and by the Ministerio de Ciencia e Innovación of Spain (AGL2011-29632). The authors are enormously grateful to Dr. Ilhem Boutiba Ben Boubaker (Antibiotic resistance laboratory, Faculty of Medicine of Tunisia) and Dr. Saadia Gargouri (Department of parasitology, Military Hospital of Tunis) for their assistance during the antimicrobial analysis and to Dr. Smaoui Abderrazek for botanical identification of the plants.

The main goal of this study was to determine the saponin profiles of different "triguero" asparagus genotypes and to compare them to green asparagus commercial hybrids. The samples consisted of 31 commercial hybrids and 58 genotypes from the Huétor-Tájar (HT) population variety ("triguero"). The saponin analysis by high-performance liquid chromatography-mass spectrometry allowed for the determination of 12 saponins derived from a furostan-type steroidal genin, 4 of which had never been described in the edible part of asparagus. The saponin profile of "triguero" asparagus was a combination of these new saponins and protodioscin. Although protodioscin was the major saponin found in commercial hybrids, some of these 12 saponins were detected as major components in some of the commercial hybrids. The total contents of saponins described in some of these HT genotypes reach values as high as 10-100 times higher than those found in commercial hybrids.

The main goal of this study was the optimization of a HPLC-MS method for the qualitative and quantitative analysis of asparagus saponins. The method includes extraction with aqueous ethanol, cleanup by solid phase extraction, separation by reverse phase chromatography, electrospray ionization, and detection in a single quadrupole mass analyzer. The method was used for the comparison of selected genotypes of Huétor-Tájar asparagus landrace and selected varieties of commercial diploid hybrids of green asparagus. The results showed that while protodioscin was almost the only saponin detected in the commercial hybrids, eight different saponins were detected in the Huétor-Tájar asparagus genotypes. The mass spectra indicated that HT saponins are derived from a furostan type steroidal genin having a single bond between carbons 5 and 6 of the B ring. The total concentration of saponins was found to be higher in triguero asparagus than in commercial hybrids.

Postprandial triglyceride (TG)-rich lipoproteins (TRLs) transport dietary fatty acids through the circulatory system to satisfy the energy and structural needs of the tissues. However, fatty acids are also able to modulate gene expression and/or induce cell death. We investigated the underlying mechanism by which postprandial TRLs of different fatty acid compositions can induce cell death in human monocytes. Three types of dietary fat [refined olive oil (ROO), high-palmitic sunflower oil (HPSO), and butter] with progressively increasing SFA:MUFA ratios (0.18, 0.41, and 2.08, respectively) were used as a source of postprandial TRLs (TRL-ROO, TRL-HPSO, and TRL-BUTTER) from healthy men. The monocytic cell line THP-1 was used as a model for this study. We demonstrated that postprandial TRLs increased intracellular lipid accumulation (31-106%), reactive oxygen species production (268-349%), DNA damage (133-1467%), poly(ADP-ribose) polymerase 1 (800-1710%) and caspase-3 (696-1244%) activities, and phosphorylation of c-Jun NH2-terminal kinase (JNK) (54 kDa, 141-288%) and p38 (24-92%). These effects were significantly greater with TRL-BUTTER, and TRL-ROO did not induce DNA damage, DNA fragmentation, or p38 phosphorylation. In addition, blockade of p38, but not of JNK, significantly decreased intracellular lipid accumulation and increased cell death in postprandial TRL-treated cells. These results suggest that in human monocytes, p38 is involved in survival signaling pathways that protect against the lipid-mediated cytotoxicity induced by postprandial TRLs that are abundant in saturated fatty acids.

The aim of this work was to study the saponin profiles from spears of different wild asparagus species in the context of its genetic diversity aside from geographical seed origin. They included Asparagus pseudoscaber Grecescu, Asparagus maritimus (L.) Mill., Asparagus brachiphyllus Turcz., Asparagus prostrates Dumort., and Asparagus officinalis L. The saponin analysis by LC-MS has shown that saponin profile from wild asparagus is similar to that previously described for triguero asparagus from Huétor-Tájar landrace (triguero HT), which had not ever been reported in the edible part of asparagus. All the samples, except A. officinalis, were characterized for having saponins distinct to protodioscin and the total saponin contents were 10-fold higher than those described for commercial hybrids of green asparagus. In particular, A. maritimus from different origins were rich in saponins previously found in triguero HT. These findings supported previous suggestion, based on genetic analysis, about A. maritimus being the origin of triguero HT. Multivariate statistics including principal component analysis and hierarchical clustering analysis were used to define both similarities and differences among samples. The results showed that the greatest variance of the tested wild asparagus could be attributed to differences in the concentration of particular saponins and this knowledge could be a tool for identifying similar species.

The incidence of high blood pressure (BP) along with other cardiovascular (CV) risk factors on human health has been studied for many years. These studies have proven a link between unhealthy dietary habits and sedentary lifestyle with the onset of hypertension, which is a hallmark of CV and cerebrovascular diseases. The Mediterranean diet, declared by the UNESCO as an Intangible Cultural Heritage since 2013, is rich in vegetables, legumes, fruits and virgin olive oil. Thanks to its many beneficial effects, including those with regard to lowering BP, the Mediterranean diet may help people from modern countries to achieve a lower occurrence of CV disease. Data from human and animal studies have shown that the consumption of virgin olive oil shares most of the beneficial effects of the Mediterranean diet. Virgin olive oil is the only edible fat that can be consumed as a natural fruit product with no additives or preservatives, and contains a unique constellation of bioactive entities, namely oleic acid and minor constituents. In this review, we summarize what is known about the effects of virgin olive oil on hypertension., This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO. AGL2011-29008) and the Conserjería de Economía, Innovación y Ciencia, Junta de Andalucía (P09-CVI-5007, Proyectos de Investigación de Excelencia). SL and SM were supported by a Juan de la Cierva contract and a FPI fellowship (BES-2012-056104) from the Spanish National Research Council (CSIC) and the MINECO, respectively. BB was supported by the “V Own Research Plan” contract from the University of Seville.

41 Páginas, 6 Figuras, 1 Tabla, The effects of steroidal saponins from edible spears of wild triguero Huetor-Tajar asparagus on some of the oncogenic molecular pathways that are affected in human colon cancer cells were investigated. Reverse-phase chromatography and a new HPLC-MS method were used to respectively isolate and analyse the composition of the steroidal saponins. They were resistant to simulated digestion and, when in contact with HTC-116 human colon carcinoma cells, interfered with extracellular signal-regulated kinase (ERK), S6 kinase (p70S6K, mTOR), and RAC-alpha serine/threonine-protein kinase (AKT) pathways by a downregulation of these proteins. The expressions of cyclins D, E, and A were also decreased, leading to G0/G1 cell cycle arrest. In addition, these steroidal saponins induced typical features of apoptosis by the promotion of caspase-3 activity, poly(ADP-ribose) polymerase 1 (PARP-1) cleavage, and DNA fragmentation. These results offer potential dietary intervention strategy against human colon cancer cells., This study was supported by grants AGL2011-29632 and AGL2011-29008 funded by MICINN. S.L. acknowledges financial support from the Spanish MINECO (JCI-2012-13084, Juan de la Cierva) and the Spanish Research Council (CSIC)/JAE-doc Program (JAEDOC089), a contract cofounded by the European Social Fund (ESF).

Aims: determine whether potential correlations between CD117 to and PDGFRA might serve as an indication for targeted therapies. Material and methods: immunohistochemical expression of CD117 and PDGFRA was evaluated in 99 paraffin-embedded GISTs in conjunction with KIT and PDGFRA mutational status. Results: CD117-positive staining was noted in 93 out of 99 cases. The predominant staining pattern was cytoplasmic, either with or without membrane accentuation; in 44.5% of cases, a clear Golgi-like pattern was evident. Correlations were found be-tween KIT mutation and both CD117 expression (p = 0.006) and Golgi-like pattern (p = 0.026). Cytoplasmic PDGFRA-positive staining was detected in 87% of cases, both with and without membrane accentuation; in 8% cases an evident Golgi-like staining pattern was observed. A significant correlation was noted between PDGFRA mutations and Golgi-like staining pattern (p = 0.001). Moreover, 95% of PDGFRA-positive GISTs were also CD117-positive, suggesting that expression of the two markers is not mutually exclusive; most of these had mutations in KIT exon 11. PDGFRA-positive/CD117-negative tumors had mutations in PDGFRA, mainly in exon 18. PDGFRA-negative/CD117-negative staining was observed in 15% of cases, all of which displayed mutations in KIT exon 11. CD117-positive/PDGFRA-negative cases were characterized by mutations in KIT, mainly in exon 11. Conclusions: CD117 and PDGFRA staining are not exclusive, and the presence of a Golgi-like staining pattern for either, whilst not pathognomonic, is highly suggestive of KIT and PDGFRA mutated GISTs, respectively, and may be used with some reservations as an alternative indication for prescribing targeted therapies.Objetivo: determinar si las posibles correlaciones entre CD117 y PDGFRA podrían servir como una indicación de terapias dirigidas. Material y métodos: la expresión inmunohistoquímica de CD117 y PDGFRA se evaluó en 99 GIST incluidos en parafina en conjunción con el estado mutacional de KIT y PDGFRA Resultados: se observó tinción CD117-positivo en 93 de los 99 casos. El patrón de tinción predominante fue citoplasmático o de membrana; en el 44,5% de los casos, se evidencio patrón de tipo Golgi. Se encontraron correlaciones entre la mutación KIT tanto con la expresión de CD117 (p = 0,006) y con el patrón tipo Golgi (p = 0,026). Se detectó tinción citoplasmática PDGFRA-positiva en el 87% de los casos, con y sin acentuación de membrana, en el 8% se observó patrón de tinción tipo Golgi. Se observó una correlación significativa entre las mutaciones PDGFRA y el patrón de tinción tipo Golgi (p = 0,001). Por otra parte, el 95% de los GIST PDGFRA positivos también fueron CD117-positivo, lo que sugiere que la expresión de los dos marcadores no se excluyen mutuamente, la mayoría de ellos tenían mutaciones en el exón 11 de KIT. Los tumores PDGFRA-positivo/CD117-negativo tenían mutaciones en PDGFRA, principalmente en el exón 18. Se observó tinción PDGFRA-negativo/CD117-negativo en el 15% de los casos, todos los cuales revelaban mutaciones en el exón 11 de KIT. Los casos CD117-positivo/PDGFRA-negativo casos se caracteriza por mutaciones en KIT, principalmente en el exón 11. Conclusiones: las tinciones CD117 y PDGFRA no son excluyentes, y la presencia de un patrón de tinción de Golgi, aunque no es patognomónica, es altamente sugestiva de GIST mutado en KIT y PDGFRA, respectivamente, y se puede utilizar con algunas reservas, como una indicación alternativa para la prescripción de terapias dirigidas.

Recurrent or metastatic GISTs are currently treated with kinase inhibitors since they achieves disease control in 70-85% of patients but this response depend on KIT and PDGFRA gene mutation status. We review the morfological and molecular findings associated to kinase inhibitors administration in GISTs based on the literature on Medline and authors' own experience. The initial response to kinase inhibitors (imatinib mesylate, Gleevec, Novartis) usually is partial and depend on the mutational KIT or PDGFRA state. Amongst patients wih KIT mutations, the best results are achived in those harboring exon 11 (85%) and exon 9 (45%) mutations. GISTs harboring PDGFRA gene mutations generally respond favorably except those involving the Asp842Val mutation. In the absence of KIT/PDGFRA gene mutations, partial response or disease stabilization is reported in 23% and 50% of patients, respectively, and disease progression in 19%. Histological examination of tumors displaying an initial response to imatinib reveals a highly-variable reduction in the number of tumor cells, a decline in the proliferative index, myxohyaline or sclerohyaline stroma, and a varying degree of bleeding and edema, necrosis and cystification. 72% of patients with initial good response to imatinib, display metastases or new nodule growth within an existing clinically-quiescent tumor after 12-36 months of treatment. This secondary resistance is characterized by a number of well-defined morphological and molecular changes. Histologically, the new growths display increased mitotic activity, pleomorphism, an epithelioid or mixed phenotype and persistent KIT expression although more rarely, dedifferentiation and loss of KIT expression (Fig. 4), as well as trans-differentiation into a rhabdomyosarcoma or epithelial phenotype has been reported. Molecularly, 46-67% of patients present additional KIT mutations, generally in the kinase domain (exons 13, 14 and 17) but also in the ATP-binding domain (exons 15,16) of the same allele. Secondary PDGFRA mutations are very rare. Secondary mutations have not been observed in GISTs not harboring KIT/PDGFRA mutations, or in tumors displaying an unusual morphology or loss of CD117 expression. A number of studies highlight the presence of different resistance mutations within different new tumor nodules, as well as the simultaneous development of distinct resistant tumor subclones within a single lesion (acquired polyclonal resistance). Secondary mutation in genes other than KIT/PDGFRA has only been reported in BRAF (Val600Glu).

The determination of flavonoid profiles from different genotypes of triguero asparagus and their comparison to those from green asparagus commercial hybrids was the main goal of this study. The samples consisted of 32 commercial hybrids and 65 genotypes from the Huetor-Tajar population variety (triguero). The analysis of individual flavonoids by HPLC-DAD-MS has allowed the determination of eight naturally occurring flavonol derivatives in several genotypes of triguero asparagus. Those compounds included mono-, di-, and triglycosides of three flavonols, that is, quercetin, isorhamnetin, and kaempferol. The detailed analysis of the flavonoid profiles revealed significant differences among the distinct genotypes. These have been classified in three distinct groups as the result of a k-means clustering analysis, two of them containing both commercial hybrids and triguero asparagus and another cluster constituted by 21 genotypes of triguero asparagus, which contain several key flavonol derivatives able to differentiate them. Hence, the triglycosides tentatively identified as quercetin-3-rhamnosyl-rutinoside, isorhamnetin-3-rhamnosyl-rutinoside, and isorhamnetin-3-O-glucoside have been detected only in the genotypes grouped in the above-mentioned cluster. On the other hand, the compound tentatively identified as isorhamnetin-3-glucosyl-rutinoside was present in most genotypes of triguero asparagus, whereas it has not been detected in any of the commercial hybrids.

White asparagus cell walls have shown to contain important amounts of phenolics, including ferulic acid and its dimers and trimers. It has been suggested that these phenolic compounds are mainly responsible for cross-linking the different cell wall polymers related to asparagus hardening. During post-harvest storage, the asparagus texture and the amount of cell wall phenolics increased significantly. In the present work, the effect of post-harvest storage conditions on the accumulation of ferulic acid and its derivatives has been investigated. Three different storage conditions were used: keeping the spears in aerobic conditions at room temperature (ART) and at 4 °C (A4 °C), and in anaerobic conditions at room temperature (AnRT). A direct relationship between phenol accumulation and increases in texture was observed, and these changes are dependent on temperature and storage atmosphere. An increase in temperature led to a higher amount of cell wall phenolics and the absence of oxygen in the storage atmosphere delayed their accumulation. The evolution of ferulic dimers during the three storage conditions suggests a relevant role of 8-O-4′-diFA and 8,5′-BAdiFA in white asparagus hardening. Copyright © 2006 Society of Chemical Industry

Cinnamic acids influence physical and textural attributes of plant foods as they play an important role in lignification and cross-linking of cell-wall polymers. Several trans-cinnamic acids have been detected in asparagus cell wall (CW), and, of these, amounts of ferulic acid (FA) and its dehydrodimers have been found to increase significantly during post-harvest storage. The distribution of these compounds along the different sections of white and green spears, as well as their modifications during postharvest storage, has been investigated. It has been observed that the cell walls from the apical, middle and lower sections of the green spears contain equivalent amounts of FA derivatives (about 400 µg g−1 CW), while these compounds are mainly located in the middle (681 µg g−1 CW) and lower section (975 µg g−1 CW) of the white ones. During asparagus post-harvest storage a general increase of FA monomers and dimers took place that affected every section of both green and white spears. Major changes occurred in the middle and lower sections of the white asparagus, where the amounts of ferulic derivatives increased to 1700 and 1678 µg g−1 CW after storage. A similar but less pronounced trend was observed for the green spears. Copyright © 2005 Society of Chemical Industry

The changes of texture that take place in white and green asparagus during storage and cooking are, in large part, determined by the composition and structure of the cell walls. Several instrumental methods have been applied to three sections of the spears to investigate the physico-chemical properties that contribute to the values of texture. Cutting the spears with a razor blade is the most appropriate method for quantifying and comparing the texture of white and green asparagus and, among the different parameters that can be calculated from the curves registered during asparagus cutting, strength and toughness have been used for determining changes of texture. Post-harvest storage caused an increase of texture mainly located in the lower portions of the white spears. The process of toughening also affected the lower section of the green spears, but to a lesser extent. Cooking resulted in a softening, mostly in the apical section of the stem. Additional information about the physico-chemical properties of different plant tissues has been obtained by applying a tensile test to the internal and external tissues separated from asparagus sections. Copyright © 2004 Society of Chemical Industry

The endogenous synthesis of lipids, which requires suitable dietary raw materials, is critical for the formation of membrane bilayers. In eukaryotic cells, phospholipids are the predominant membrane lipids and consist of hydrophobic acyl chains attached to a hydrophilic head group. The relative balance between saturated, monounsaturated, and polyunsaturated acyl chains is required for the organization and normal function of membranes. Virgin olive oil is the richest natural dietary source of the monounsaturated lipid oleic acid and is one of the key components of the healthy Mediterranean diet. Virgin olive oil also contains a unique constellation of many other lipophilic and amphipathic constituents whose health benefits are still being discovered. The focus of this review is the latest evidence regarding the impact of oleic acid and the minor constituents of virgin olive oil on the arrangement and behavior of lipid bilayers. We highlight the relevance of these interactions to the potential use of virgin olive oil in preserving the functional properties of membranes to maintain health and in modulating membrane functions that can be altered in several pathologies. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. © 2014 Elsevier B.V., We thank to the Spanish Ministry of Science and Innovation (MICINN) and the European Commission (EC) for financial support (AGL2011-29008 and Marie Curie PERG07-GA-2010-268413). S.L. and B.B. acknowledge financial support from the Spanish National Research Council (CSIC)/JAE-Doc Program, a contract cofounded by the European Social Fund (ESF). S.M. has the benefit of a FPI fellowship (BES-2012-056104) of MICINN.

© 2014 American Chemical Society. Asparagus byproducts are a good source of cationic soluble peroxidases (CAP) useful for the bioremediation of phenol-contaminated wastewaters. In this study, cell wall bound peroxidases (POD) from the same byproducts have been purified and characterized. The covalent forms of POD represent >90% of the total cell wall bound POD. Isoelectric focusing showed that whereas the covalent fraction is constituted primarily by anionic isoenzymes, the ionic fraction is a mixture of anionic, neutral, and cationic isoenzymes. Covalently bound peroxidases were purified by means of ion exchange chromatography and affinity chromatography. In vitro detoxification studies showed that although CAP are more effective for the removal of 4-CP and 2,4-DCP, anionic asparagus peroxidase (AAP) is a better option for the removal of hydroxytyrosol (HT), the main phenol present in olive mill wastewaters., S.J.-C. and S.L. acknowledge financial support from the Spanish CSIC (JAE-doc Program), a contract cofunded by the ESF. S.V.-C. thank the Spanish CSIC for her contract (JAE Pre Program).

Soluble peroxidase (POD) from asparagus byproducts was purified by ion exchange chromatographies, and its kinetic and catalytic properties were studied. The isoelectric point of the purified isoperoxidases was 9.1, and the optimum pH and temperature values were 4.0 and 25 C, respectively. The cationic asparagus POD (CAP) midpoint inactivation temperature was 57 C, which favors its use in industrial processes. The Km values of cationic asparagus POD for H2O2 and ABTS were 0.318 and 0.634 mM, respectively. The purified CAP is economically obtained from raw materials using a simple protocol and possesses features that make it advantageous for the potential use of this enzyme in a large number of processes with demonstrated requirements of thermostable POD. The results indicate that CAP can be used as a potential candidate for removing phenolic contaminants. © 2013 American Chemical Society., S.J.-C. and S.L. acknowledge financial support from Spanish CSIC (JAE-doc Program), a contract cofunded by the ESF. S.V.-C. thanks Spanish CSIC for her contract (JAE Pre Program).

Aims: determine whether potential correlations between CD117 to and PDGFRA might serve as an indication for targeted therapies. Material and methods: immunohistochemical expression of CD117 and PDGFRA was evaluated in 99 paraffin-embedded GISTs in conjunction with KIT and PDGFRA mutational status. Results: CD117-positive staining was noted in 93 out of 99 cases. The predominant staining pattern was cytoplasmic, either with or without membrane accentuation; in 44.5% of cases, a clear Golgi-like pattern was evident. Correlations were found be-tween KIT mutation and both CD117 expression (p = 0.006) and Golgi-like pattern (p = 0.026). Cytoplasmic PDGFRA-positive staining was detected in 87% of cases, both with and without membrane accentuation; in 8% cases an evident Golgi-like staining pattern was observed. A significant correlation was noted between PDGFRA mutations and Golgi-like staining pattern (p = 0.001). Moreover, 95% of PDGFRA-positive GISTs were also CD117-positive, suggesting that expression of the two markers is not mutually exclusive; most of these had mutations in KIT exon 11. PDGFRA-positive/CD117-negative tumors had mutations in PDGFRA, mainly in exon 18. PDGFRA-negative/CD117-negative staining was observed in 15% of cases, all of which displayed mutations in KIT exon 11. CD117-positive/PDGFRA-negative cases were characterized by mutations in KIT, mainly in exon 11. Conclusions: CD117 and PDGFRA staining are not exclusive, and the presence of a Golgi-like staining pattern for either, whilst not pathognomonic, is highly suggestive of KIT and PDGFRA mutated GISTs, respectively, and may be used with some reservations as an alternative indication for prescribing targeted therapies.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Expression of CD117, DOG1 and PKCθ was investigated immunohistochemically in a series of 99 paraffin-embedded GISTs in order to determine the sensitivity and diagnostic value of these markers. KIT exons 9, 11, 13 and 17 and PDGFRA exons 12 and 18 were amplified by PCR and sequenced. A total of 94/99 (94%) GISTs stained positive for CD117, 81/99 (82%) for PKCθ and 90/99 (91%) for DOG-1. A significant correlation was noted between CD117 and DOG-1 expression (p=0.0001). All three markers were expressed in 74% (73/99) of GISTs. Of the five CD117-negative cases, two were PKCθ-negative/DOG1-negative and had mutations in KIT exon 11. Two were PKCθ-positive/DOG1-positive and had mutations in PDGFRA (one each in exons 12 and 18), and one was DOG1-negative/PKCθ-positive, with a PDGFRA exon 18 mutation. The most sensitive marker was CD117, followed by DOG-1 and PKCθ. Although PKCθ was less sensitive, and its staining is more challenging and difficult to interpret, the use of this marker is highly recommended, particularly in CD117-negative/DOG-1-negative GISTs.

The aim of this study was to determine whether isorhamnetin, an immediate 3′-O-methylated metabolite of quercetin, affects proliferation, cell death, and the cell cycle of human colon carcinoma (HCT-116) cells. Isorhamnetin was found to be a potent antiproliferative agent in a dose- and time-dependent manner, with an IC50 of 72 μM after 48 h of incubation as estimated by MTT assay. Flow cytometry and fluorescence microscopy analysis showed that isorhamnetin exerted a stimulatory effect on apoptosis and necrosis. Isorhamnetin also increased the number of cells in G2/M phase. Serum deprivation appeared to potentiate the effects of isorhamnetin on cell death and facilitated cell cycle progression to G0/G1 phase. These results suggest that isorhamnetin might mediate inhibition of HCT-116 cell growth through the perturbation of cell cycle progression and are consistent with the notion that G2/M checkpoints could be a conserved target for flavonoids in human colon cancer cells, leading to apoptotic and necrotic death. These antiproliferative, apoptotic, necrotic, and cell cycle effects suggest that isorhamnetin may have clinically significant therapeutic and chemopreventive capabilities. To our knowledge, this is the first report of the effect of isorhamnetin on human colon cancer cells., This work was supported by Grant AGL2007-63703 from the Ministerio de Ciencia e Innovación (MICINN).

Asparagus (Asparagus officinalis L.) by-products, which represent around 50% of the processed vegetable, are a potential source of dietary fibre. The way that these by-products are treated affects the composition and functional properties of fibre-rich powders. Factors such as treatment intensity, solvent, and drying system were studied. Only the more soluble components (soluble sugars, uronic acids and proteins) showed significant differences. All the fibre-rich powders had high concentrations of TDF (62–77%). The IF/SF proportion decreased with the severity of treatment, in this way increasing the physiological quality of the fibre. Functional properties, namely water-holding capacity (WHC), oil-holding capacity (OHC), solubility (SOL), and glucose dialysis retardation index (GDRI), varied according to the preparation procedure. WHC and GDRI were higher in intensely extracted fibres; due to the effect of thermal processing. WHC showed values (11–20 ml water/g powder) similar to those described for other agricultural by-products, but OHC and GDRI were much higher (5–8 ml oil/g powder and 25–45%, respectively). These properties make fibre-rich powders from asparagus by-products a valuable source of dietary fibre to be included in the formulation of fibre-enriched foods., This research was supported by the Ministerio de Ciencia y Tecnología (Spain), Proyect PETRI PTR1995-0968-OP.

Asparagus (Asparagus officinalis L.) spears are highly appreciated for their composition of bioactive compounds. The method by which their by-products are treated affects the phytochemical composition and antioxidant activity of the fibre-rich powders. Factors such as the treatment intensity, the solvent used, and the drying system were studied. Among the asparagus phytochemicals, hydroxycinnamic acids (HCA), saponins, flavonoids, sterols, and fructans were quantified. HCA varied from 2.31 and 4.91 mg/g of fibre, the content being affected by the drying system and, in some cases, the solvent. Fibres from intense treatments had significantly higher amounts of saponin than samples isolated by gentle treatments. Saponin content ranged from 2.14 to 3.64 mg/g of fibre. Flavonoids were the most affected by processing conditions, being present (0.6–1.8 mg/g of fibre) only in three of the samples analysed. Continuous stirring during processing could be the main reason for this result. Sterols and fructans were present in minor amounts, 0.63–1.03 mg/g of fibre and 0.2–1.4 mg/g of fibre, respectively. Soluble and total antioxidant activities were also measured. Fibres with the highest activities corresponded to those with the highest levels of flavonoids and HCA., This research was supported by the Ministerio de Ciencia y Tecnología (Spain), Proyect PETRI PTR1995-0968-OP, and Centro Sur S.C.A. (Huétor-Tajar, Granada, Spain).

The presence of 3,4-dihydroxyphenylglycol (DHPG) was studied in 32 samples and 10 different cultivars of natural table olives, using an accurate method to avoid wrong quantification. Hydroxytyrosol (HT), tyrosol, and verbascoside were also quantified, as these four compounds comprise the majority of the chromatographic profile. Analyses were carried out by HPLC-DAD-UV after extraction of all phenolics, and hydroxytyrosol was the major component in nearly all samples. High levels of DHPG (up to 368 mg/kg of dry weight) were found in the pulp of natural black olives independent of cultivar and processing method, similar to its concentration in the brine in almost all of the samples. The presented data for this antioxidant indicate that natural table olives are a rich source of DHPG and hydroxytyrosol, compounds with interesting nutritional and antioxidant properties., This work was supported by the Ministerio de Educación y Ciencia through Grants AGL2005-00616-ALi/AGL2008-02590-ALI and AGL2007-66373-CO4-01-ALI. We thank the Junta de Andalucía (PO6-AGR-01906) for financial support.

En este artículo se desglosan los diversos procesos que se han seguido en el desarrollo del Proyecto Écija (Sevilla), haciendo especial hincapié en los estudios previos y planificación, las herramientas utilizadas, elementos técnicos empleados y los procesos de investigación y actualización de datos en la descripción de los inmuebles que se presentan, desarrollados a través de itinerarios culturales por tipologías de edificios e imbricados en el territorio en donde se ubican

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La elaboración de un CD-ROM multimedia como producto de difusión del Patrimonio Histórico Andaluz, con recursos técnicos y humanos propios, viene siendo desde hace años una aspiración constante del Departamento de Técnicas de Documentación Gráfica del Centro de Documentación del IAPH. En este contexto y en el seno de dicho Departamento se ha gestado el Proyecto sobre el Patrimonio Inmueble de Écija, como paradigma de una ciudad histórica de tipo medio, con el auxilio de un equipomultidisciplinar de trabajo generado en el propio Centro de Documentación. En este avance exponemos los principales escollos de tipo técnico que han surgido y, de forma especial, la estructuración de los contenidos y la definición de una metodología-marco a seguir en futuros trabajos de esta misma índole.

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Previous studies on bioactive components of asparagus have revealed that the by-products are rich in many of the phytochemicals located in the edible part of the spears. The main components responsible of asparagus bioactivity are phenols (flavonoids and hydroxycinnamic acids) and saponins. We have developed a process for obtaining added-value compounds from asparagus by-products by the hydrothermal treatment of the samples. Two fractions are separated after the hydrothermal treatment, consisting on an aqueous functional extract containing most soluble bioactive compounds from asparagus by-product, and a fibrous residue that, after being dried, constitutes the asparagus bioactive fibre. The process includes a column purification step, using an adsorbent polymeric resin, which allows aqueous extracts, partially purified to be obtained and enriched in specific compounds (phenolics and/or saponins). All these presentations have been investigated for their biological activity. The preliminary results showed that the distinct products obtained from asparagus by-products are of interest for their biological activity and are suitable for being used as functional ingredients. Based on their antioxidant capacity, it could be proposed that their regular use could help the prevention of several diseases related to the oxidative damage.

Fuente TESIUNAM

Fuente TESIUNAM

Fuente TESIUNAM