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Compared Binding Properties between Resveratrol and Other Polyphenols to Plasmatic Albumin: Consequences for the Health Protecting Effect of Dietary Plant Microcomponents.
Molecules
PUBLISHED: 08-30-2014
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Phytophenols are considered to have beneficial effects towards human physiology. They are food microcomponents with potent chemopreventive properties towards the most three frequent contemporary human diseases, e.g., cardiovascular alterations, cancer and neurodegenerative pathologies. Related to this, the plasmatic form and plasmatic level of plant polyphenols in the body circulation are crucial for their efficiency. Thus, determinations of the binding process of resveratrol and of common flavonoids produced by major edible plants, berries and fruits to plasma proteins are essential. The interactions between resveratrol and albumin, a major plasma protein, were compared with those already published, involving curcumin, genistein, quercetin and other well-known food-containing polyphenols. The approaches used are usually intrinsic fluorescence intensity changes, quenching of protein intrinsic fluorescence and infrared spectroscopy. It appears that: (1) all of the studied polyphenols interact with albumin; (2) while most of the studied polyphenols interact at one albumin binding site, there are two different types of resveratrol binding sites for bovine serum albumin, one with the highest affinity (apparent KD of 4 µM) with a stoichiometry of one per monomer and a second with a lower affinity (apparent KD of 20 µM) with also a stoichiometry of one per monomer; (3) at least one binding site is in the vicinity of one tryptophanyl residue of bovine serum albumin; and (4) resveratrol binding to bovine serum albumin produces a very small structural conformation change of the polypeptide chain. These results support a role played by polyphenols-albumin interactions in the plasma for the bio-activities of these food microcomponents in the body.
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Comprehensive CFTR gene analysis of the French cystic fibrosis screened newborn cohort: implications for diagnosis, genetic counseling, and mutation-specific therapy.
Genet. Med.
PUBLISHED: 08-14-2014
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Purpose:Newborn screening (NBS) for cystic fibrosis (CF) was implemented throughout France in 2002. It involves a four-tiered procedure: immunoreactive trypsin (IRT)/DNA/IRT/sweat test was implemented throughout France in 2002. The aim of this study was to assess the performance of molecular CFTR gene analysis from the French NBS cohort, to evaluate CF incidence, mutation detection rate, and allelic heterogeneity.Methods:During the 8-year period, 5,947,148 newborns were screened for cystic fibrosis. The data were collected by the Association Française pour le Dépistage et la Prévention des Handicaps de l'Enfant. The mutations identified were classified into four groups based on their potential for causing disease, and a diagnostic algorithm was proposed.Results:Combining the genetic and sweat test results, 1,160 neonates were diagnosed as having cystic fibrosis. The corresponding incidence, including both the meconium ileus (MI) and false-negative cases, was calculated at 1 in 4,726 live births. The CF30 kit, completed with a comprehensive CFTR gene analysis, provides an excellent detection rate of 99.77% for the mutated alleles, enabling the identification of a complete genotype in 99.55% of affected neonates. With more than 200 different mutations characterized, we confirmed the French allelic heterogeneity.Conclusion:The very good sensitivity, specificity, and positive predictive value obtained suggest that the four-tiered IRT/DNA/IRT/sweat test procedure may provide an effective strategy for newborn screening for cystic fibrosis.Genet Med advance online publication 14 August 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.113.
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Inhibition of cancer derived cell lines proliferation by synthesized hydroxylated stilbenes and new ferrocenyl-stilbene analogs. Comparison with resveratrol.
Molecules
PUBLISHED: 04-29-2014
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Further advances in understanding the mechanism of action of resveratrol and its application require new analogs to identify the structural determinants for the cell proliferation inhibition potency. Therefore, we synthesized new trans-resveratrol derivatives by using the Wittig and Heck methods, thus modifying the hydroxylation and methoxylation patterns of the parent molecule. Moreover, we also synthesized new ferrocenylstilbene analogs by using an original protective group in the Wittig procedure. By performing cell proliferation assays we observed that the resveratrol derivatives show inhibition on the human colorectal tumor SW480 cell line. On the other hand, cell viability/cytotoxicity assays showed a weaker effects on the human hepatoblastoma HepG2 cell line. Importantly, the lack of effect on non-tumor cells (IEC18 intestinal epithelium cells) demonstrates the selectivity of these molecules for cancer cells. Here, we show that the numbers and positions of hydroxy and methoxy groups are crucial for the inhibition efficacy. In addition, the presence of at least one phenolic group is essential for the antitumoral activity. Moreover, in the series of ferrocenylstilbene analogs, the presence of a hidden phenolic function allows for a better solubilization in the cellular environment and significantly increases the antitumoral activity.
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A role for peroxisome proliferator-activated receptor gamma in resveratrol-induced colon cancer cell apoptosis.
Mol Nutr Food Res
PUBLISHED: 03-31-2014
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Resveratrol may function as a chemopreventive agent. A recent clinical study demonstrates a reduction in tumor cell proliferation in colorectal patients receiving repeated oral ingestion of resveratrol. However, gaps remain in our knowledge of the molecular mechanisms by which resveratrol exerts its chemopreventive effect. We have previously demonstrated that resveratrol induces apoptosis in colon cancer cells and that resveratrol can sensitize chemoresistant colon cancer cells to various drugs. Based on its ability to activate peroxisome proliferator-activated receptor gamma (PPAR?) in colon cancer cells, we sought to determine the implication of this nuclear transcription factor in resveratrol-induced apoptosis.
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Differential protective effects of red wine polyphenol extracts (RWEs) on colon carcinogenesis.
Food Funct
PUBLISHED: 02-27-2014
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Various epidemiological studies have shown that a regular and moderate consumption of red wine is correlated with a decreased relative risk of developing coronary heart disease and cancer. These health benefits are commonly attributed to high contents of polyphenols, particularly resveratrol, representing important sources of antioxidants. However, resveratrol does not seem to be the only bioactive compound present in the wine which contains numerous other polyphenols. The present study investigates the efficiency of red wine extracts (RWEs), containing different polyphenols, on colon cancer cell proliferation in vitro and on colonic aberrant crypt foci (ACF) in vivo. Proliferation, cell cycle analysis and incidence of ACF were monitored to examine the effects of RWEs. RWEs derived from a long vinification process exhibit superior anti-proliferative activity in colon cancer cells and prevent the appearance of ACF in mice. Interestingly, quercetin and resveratrol, representing two major bio-active polyphenols, exhibit synergistic anti-proliferative effects. These data suggest that the efficacy of RWEs on colon carcinogenesis may depend on the polyphenolic content, synergistic interaction of bio-active polyphenols and modulation of cellular uptake of polyphenols.
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Stilbenes and resveratrol metabolites improve mitochondrial fatty acid oxidation defects in human fibroblasts.
Orphanet J Rare Dis
PUBLISHED: 02-20-2014
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Inborn enzyme defects of mitochondrial fatty acid beta-oxidation (FAO) form a large group of genetic disorders associated to variable clinical presentations ranging from life-threatening pediatric manifestations up to milder late onset phenotypes, including myopathy. Very few candidate drugs have been identified in this group of disorders. Resveratrol (RSV) is a natural polyphenol with anti-oxidant and anti-inflammatory effects, recently shown to have beneficial metabolic properties in mice models. Our study explores its possible effects on FAO and mitochondrial energy metabolism in human cells, which are still very little documented.
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The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk.
Front Public Health
PUBLISHED: 01-01-2014
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The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10-24?years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people.
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Importance of lipid microdomains, rafts, in absorption, delivery, and biological effects of resveratrol.
Ann. N. Y. Acad. Sci.
PUBLISHED: 07-17-2013
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The preventive effects of the phytoalexin trans-resveratrol toward cancer have been largely described at the cellular and molecular levels in both in vivo and in vitro models; however, its primary targets are still poorly identified. In this review, we show the crucial role of cell membrane microdomains, that is, lipid rafts, not solely in the initiation of the early biochemical events triggered by resveratrol leading to cancer cell death, but also in resveratrol absorption and distribution. Resveratrol accumulates in lipid rafts and is then taken up by cells through raft-dependent endocytosis. These events allow early activation of kinase pathways and redistribution of cell death receptors within lipid microdomains, events ultimately leading to apoptotic cell death.
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Mechanisms of ceramide-induced COX-2-dependent apoptosis in human ovarian cancer OVCAR-3 cells partially overlapped with resveratrol.
J. Cell. Biochem.
PUBLISHED: 02-28-2013
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Ceramide is a member of the sphingolipid family of bioactive molecules demonstrated to have profound, diverse biological activities. Ceramide is a potential chemotherapeutic agent via the induction of apoptosis. Exposure to ceramide activates extracellular-signal-regulated kinases (ERK)1/2- and p38 kinase-dependent apoptosis in human ovarian cancer OVCAR-3 cells, concomitant with an increase in the expression of COX-2 and p53 phosphorylation. Blockade of cyclooxygenase-2 (COX-2) activity by siRNA or NS398 correspondingly inhibited ceramide-induced p53 Ser-15 phosphorylation and apoptosis; thus COX-2 appears at the apex of the p38 kinase-mediated signaling cascade induced by ceramide. Induction of apoptosis by ceramide or resveratrol was inhibited by the endocytosis inhibitor, cytochalasin D (CytD); however, cells exposed to resveratrol showed greater sensitivity than ceramide-treated cells. Ceramide-treated cells underwent a dose-dependent reduction in trans-membrane potential. Although both ceramide and resveratrol induced the expressions of caspase-3 and -7, the effect of inducible COX-2 was different in caspase-7 expression induced by ceramide compared to resveratrol. In summary, resveratrol and ceramide converge on an endocytosis-requiring, ERK1/2-dependent signal transduction pathway and induction of COX-expression as an essential molecular antecedent for subsequent p53-dependent apoptosis. In addition, expressions of caspase-3 and -7 are observed. However, a p38 kinase-dependent signal transduction pathway and change in mitochondrial potential are also involved in ceramide-induced apoptosis.
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Absence of correlation between oxysterol accumulation in lipid raft microdomains, calcium increase, and apoptosis induction on 158N murine oligodendrocytes.
Biochem. Pharmacol.
PUBLISHED: 02-25-2013
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There is some evidence that oxidized derivatives of cholesterol, 7-ketocholesterol (7KC) and 7?-hydroxycholesterol (7?OHC), are increased in the plasma of patients with neurodegenerative diseases associated with demyelinization of the central nervous system (CNS). It was therefore of interest to investigate the effects of these oxysterols on oligodendrocytes, the myelin-forming cells in the CNS. To this end, 158N murine oligodendrocytes were treated with 7KC or 7?OHC inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving Mcl-1, and caspase-3 activation. In contrast, under treatment with 27-hydroxycholesterol (27OHC), no cell death was observed. When the cells were stained with Fura-2, no significant Ca(2+) rise was found with the different oxysterols, whereas strong signals were detected with ionomycin used as positive control. At concentrations which induced apoptosis, 7KC but not 7?OHC accumulated in lipid rafts. Although not cytotoxic, 27OHC was mainly detected in lipid rafts. It is noteworthy that ?-tocopherol (but not ellagic acid and resveratrol) was able to counteract 7KC- and 7?OHC-induced apoptosis and to decrease the accumulation of 7KC and 27OHC in lipid rafts. Thus, in 158N cells, the ability of oxysterols to trigger a mode of cell death by apoptosis involving GSK-3 and caspase-3 activation is independent of the increase in the Ca(2+) level and of their accumulation in lipid raft microdomains.
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Resveratrol metabolites inhibit human metastatic colon cancer cells progression and synergize with chemotherapeutic drugs to induce cell death.
Mol Nutr Food Res
PUBLISHED: 01-03-2013
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Resveratrol (RSV) has been proposed to prevent tumor growth; nevertheless, these preventive effects are controversial since RSV pharmacokinetics studies show a low bioavailability. Recent clinical trials show that patients with colorectal cancer and receiving oral RSV have high levels of RSV conjugates in the colorectum, mainly RSV-3-O-sulfate (R3S), RSV-3-O-glucuronide, and RSV-4-O-glucuronide. However, their potential biological activity has not yet been established. This study thus investigated in human colorectal cancer cell lines whether RSV main metabolites retain anticarcinogenic properties as their parental molecule.
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Pro-apoptotic versus anti-apoptotic properties of dietary resveratrol on tumoral and normal cardiac cells.
Genes Nutr
PUBLISHED: 04-21-2011
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Resveratrol is a natural dietary polyphenol found in grape skin, red wine, and various other food products. Resveratrol has proved to be an effective chemopreventive agent for different malignant tumors. It has also been shown to prevent vascular alterations such as atherosclerosis and inflammatory-associated events. In view of these observations, we investigated the anti-proliferative and pro-apoptotic activities of resveratrol on a tumoral cardiac cell line (HL-1 NB) derived from mouse tumoral atrial cardiac myocytes. These effects were compared with those found on normal neonatal mouse cardiomyocytes. HL-1 NB cells and neonatal cardiomyocytes were treated with resveratrol (5, 30, and/or 100 ?M) for different times of culture (24, 48, and/or 72 h). Resveratrol effects were determined by various microscopical and flow cytometric methods. After resveratrol treatment, a strong inhibition of tumoral cardiac HL1-NB cell growth associated with a loss of cell adhesion was observed. This cell proliferation arrest was associated with an apoptotic process revealed by an increased percentage of cells with fragmented and/or condensed nuclei (characteristic of apoptotic cells) identified after staining with Hoechst 33342 and by the presence of cells in subG1. At the opposite, on normal cardiomyocytes, no cytotoxic effects of resveratrol were observed, and a protective effect of resveratrol against norepinephrine-induced apoptosis was found on normal cardiomyocytes. Altogether, the present data demonstrate that resveratrol (1) induces apoptosis of tumoral cardiac HL1-NB cells, (2) does not induce cell death on normal cardiomyocytes, and (3) prevents norepinephrine-induced apoptosis on normal cardiomyocytes.
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Endocytosis of resveratrol via lipid rafts and activation of downstream signaling pathways in cancer cells.
Cancer Prev Res (Phila)
PUBLISHED: 04-05-2011
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trans-Resveratrol has been proposed to prevent tumor growth and to sensitize cancer cells to anticancer agents. Polyphenol entry into the cells has remained poorly understood. Here, we show that [(3)H]-resveratrol enters colon cancer cells (SW480, SW620, HT29) and leukemia U937 cells through a monensin (5-20 ?mol/L) -sensitive process that suggests clathrin-independent endocytosis. Uptake of the molecule can be prevented by methyl-?-cyclodextrin (2-12 mg/mL), nystatin (12 ng/mL), and filipin (1 ?g/mL), which all disrupt plasma membrane lipid rafts. Accordingly, radiolabeled resveratrol accumulates in sphingomyelin- and cholesterol-enriched cell fractions. Interestingly, extracellular signal-regulated kinases (ERK), c-Jun NH(2)-terminal kinases (JNK), and Akt also accumulate in lipid rafts on resveratrol exposure (IC(50) at 48 h ? 30 ?mol/L in SW480 and U937 cells). In these rafts also, resveratrol promotes the recruitment, by the integrin ?(V)?(3) (revealed by coimmunoprecipitation with an anti-integrin ?(V)?(3) antibody), of signaling molecules that include the FAK (focal adhesion kinase), Fyn, Grb2, Ras, and SOS proteins. Resveratrol-induced activation of downstream signaling pathways and caspase-dependent apoptosis is prevented by endocytosis inhibitors, lipid raft-disrupting molecules, and the integrin antagonist peptide arginine-glycine-aspartate (500 nmol/L). Altogether, these data show the role played by lipid rafts in resveratrol endocytosis and activation of downstream pathways leading to cell death.
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Role of membrane dynamics processes and exogenous molecules in cellular resveratrol uptake: consequences in bioavailability and activities.
Mol Nutr Food Res
PUBLISHED: 01-28-2011
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In the fields of nutrition prevention and therapy treatment, numerous studies have reported interesting properties of trans-resveratrol (RSV), a natural polyphenol against pathologies such as vascular diseases, cancers, viral infections and neurodegenerative processes. These beneficial effects are supported by more studies showing the pleiotropic actions of RSV. Nevertheless, a crucial question concerning these effects is how the polyphenol, when applied to an organism, gains access to its targets. In this review, we focus on the biochemical and biological parameters involved in RSV transport, particularly the role of the phospholipid bilayer in RSV uptake (passive diffusion, carrier-mediated transport) and of exogenous molecules modulating RSV transport and effects. The dynamic processes of the plasma membrane reveal the importance of the role of lipid composition in the fluidity, the lipid rafts in RSV endocytosis and the ATP-binding cassette transporters in RSV efflux. Specific membrane receptors such as integrin ?v?3 contribute to RSV uptake and to activate signalling pathways involved in apoptosis. We discuss the role of intracellular receptors (i.e. aryl-hydrocarbon and estrogen receptors). In addition, circulating molecules (i.e. albumin, haemoglobin, fatty acids, lipoproteins) play a role as RSV carriers. Finally, we developed a hypothesis concerning the relation between RSV uptake and its biological activities.
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?-Tocopherol impairs 7-ketocholesterol-induced caspase-3-dependent apoptosis involving GSK-3 activation and Mcl-1 degradation on 158N murine oligodendrocytes.
Chem. Phys. Lipids
PUBLISHED: 01-26-2011
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In important and severe neurodegenerative pathologies, 7-ketocholesterol, mainly resulting from cholesterol autoxidation, may contribute to dys- or demyelination processes. On various cell types, 7-ketocholesterol has often been shown to induce a complex mode of cell death by apoptosis associated with phospholipidosis. On 158N murine oligodendrocytes treated with 7-ketocholesterol (20 ?g/mL corresponding to 50 ?M, 24-48 h), the induction of a mode of cell death by apoptosis characterised by the occurrence of cells with condensed and/or fragmented nuclei, caspase activation (including caspase-3) and internucleosomal DNA fragmentation was observed. It was associated with a loss of transmembrane mitochondrial potential (??m) measured with JC-1, with a dephosphorylation of Akt and GSK3 (especially GSK3?), and with degradation of Mcl-1. With ?-tocopherol (400 ?M), which was capable of counteracting 7-ketocholesterol-induced apoptosis, Akt and GSK3? dephosphorylation were inhibited as well as Mcl-1 degradation. These data underline that the potential protective effects of ?-tocopherol against 7-ketocholesterol-induced apoptosis do not depend on the cell line considered, and that the cascade of events (Akt/GSK3?/Mcl-1) constitutes a link between 7-ketocholesterol-induced cytoplasmic membrane dysfunctions and mitochondrial depolarisation leading to apoptosis.
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Transport, stability, and biological activity of resveratrol.
Ann. N. Y. Acad. Sci.
PUBLISHED: 01-26-2011
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Numerous studies have reported interesting properties of trans-resveratrol, a phytoalexin, as a preventive agent of several important pathologies: vascular diseases, cancers, viral infections, and neurodegenerative processes. These beneficial effects of resveratrol have been supported by observations at the cellular and molecular levels in both cellular and in vivo models, but the cellular fate of resveratrol remains unclear. We suggest here that resveratrol uptake, metabolism, and stability of the parent molecule could influence the biological effects of resveratrol. It appears that resveratrol stability involves redox reactions and biotransformation that influence its antioxidant properties. Resveratrols pharmacokinetics and metabolism represent other important issues, notably, the putative effects of its metabolites on pathology models. For example, some metabolites, mainly sulfate-conjugated resveratrol, show biological effects in cellular models. The modifications of resveratrol stability, chemical structure, and metabolism could change its cellular and molecular targets and could be crucial for improving or decreasing its chemopreventive properties.
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What is new for an old molecule? Systematic review and recommendations on the use of resveratrol.
PLoS ONE
PUBLISHED: 01-21-2011
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Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark.
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Structural basis for the potential antitumour activity of DNA-interacting benzo[kl]xanthene lignans.
Org. Biomol. Chem.
PUBLISHED: 11-16-2010
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The biological properties and possible pharmacological applications of benzo[kl]xanthene lignans, rare among natural products and synthetic compounds, are almost unexplored. In the present contribution, the possible interaction of six synthetic benzo[kl]xanthene lignans and the natural metabolite rufescidride with DNA has been investigated through a combined STD-NMR and molecular docking approach, paralleled by in vitro biological assays on their antiproliferative activity towards two different cancer cell lines: SW 480 and HepG2. Our data suggest that the benzo[kl]xanthene lignans are suitable lead compounds for the design of DNA selective ligands with potential antitumour properties.
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Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD.
Carcinogenesis
PUBLISHED: 07-09-2010
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An inflammatory component is present in the microenvironment of most neoplastic tissues, including those not causally related to an obvious inflammatory process. Several microRNAs, and especially miR-155, play an essential role in both the innate and adaptative immune response. Resveratrol (trans-3,4,5-trihydroxystilbene) is a natural antioxidant with anti-inflammatory properties that is currently at the stage of preclinical studies for human cancer prevention. Here, we establish that, in human THP-1 monocytic cells as well as in human blood monocytes, resveratrol upregulates miR-663, a microRNA potentially targeting multiple genes implicated in the immune response. In THP-1 cells, miR-663 decreases endogenous activator protein-1 (AP-1) activity and impairs its upregulation by lipopolysaccharides (LPS), at least in part by directly targeting JunB and JunD transcripts. We further establish that the downregulation of AP-1 activity by resveratrol is miR-663 dependent and that the effects of resveratrol on both AP-1 activity and JunB levels are dose dependent. Finally, we show that resveratrol impairs the upregulation of miR-155 by LPS in a miR-663-dependent manner. Given the role of miR-155 in the innate immune response and the fact that it is upregulated in many cancers, our results suggest that manipulating miR-663 levels may help to optimize the use of resveratrol as both an anti-inflammatory and anticancer agent against malignancies associated with high levels of miR-155.
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Assessment of hand bone loss in rheumatoid arthritis by high-resolution peripheral quantitative CT.
Ann. Rheum. Dis.
PUBLISHED: 06-04-2010
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A new high-resolution peripheral quantitative CT (HR-pQCT) system allows for in vivo assessment of bone microarchitecture and volumetric bone mineral density (vBMD) with an 82 microm isotropic resolution. With this device, the microarchitecture impairment was evaluated in patients with rheumatoid arthritis (RA) in comparison with healthy controls and measured the erosion volume at metacarpal heads (MCPs).
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Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGF? signaling pathway in SW480 cells.
Biochem. Pharmacol.
PUBLISHED: 04-30-2010
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Resveratrol (trans-3,4,5-trihydroxystilbene) is a natural antioxidant with cardiovascular and cancer preventive properties that is currently at the stage of pre-clinical studies for human cancer prevention. Beside its known effects on protein coding genes, one possible mechanism for resveratrol protective activities is by modulating the levels of non-coding RNAs. Here, we analyzed the effects of resveratrol on microRNA populations in human SW480 colon cancer cells. We establish that resveratrol treatment decreases the levels of several oncogenic microRNAs targeting genes encoding Dicer1, a cytoplasmic RNase III producing mature microRNAs from their immediate precursors, tumor-suppressor factors such as PDCD4 or PTEN, as well as key effectors of the TGF? signaling pathway, while increasing the levels of miR-663, a tumor-suppressor microRNA targeting TGF?1 transcripts. We also show that, while upregulating several components of the TGF? signaling pathway such as TGF? receptors type I (TGF?R1) and type II (TGF?R2), resveratrol decreases the transcriptional activity of SMADs, the main effectors of the canonical TGF? pathway. Our results establish that protective properties of resveratrol may arise at least in part from its capability to modify the composition of microRNA populations in cells, and suggest that the manipulation of the levels of key microRNAs, such as miR-663, may help to potentiate the anti-cancer and anti-metastatic effects of resveratrol.
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Structural determinants of resveratrol for cell proliferation inhibition potency: experimental and docking studies of new analogs.
Eur J Med Chem
PUBLISHED: 03-15-2010
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Resveratrol is the subject of intense research because of the abundance of this compound in the human diet and as one of the most valuable natural chemopreventive agents. Further advances require new resveratrol analogs be used to identify the structural determinants of resveratrol for the inhibition potency of cell proliferation by comparing experimental and docking studies. Therefore, we synthesized new trans/(E)- and cis/(Z)-resveratrol - analogs not reported to date - by modifying the hydroxylation pattern of resveratrol and a double bond geometry. We included them in a larger panel of 14 molecules, including (Z)-3,5,4-trimethoxystilbene, the most powerful molecule that is used as reference. Using a docking model complementary to experimental studies on the proliferation inhibition of the human colorectal tumor SW480 cell line, we show that methylation is the determinant substitution in inhibition efficacy, but only in molecules bearing a Z configuration. Most of the synthetic methylated derivatives (E or Z) stop mitosis at the M phase and lead to polyploid cells, while (E)-resveratrol inhibits cells at the S phase. Docking studies show that almost all of the docked structures of (Z)-polymethoxy isomers, but not most of the (E)-polymethoxy isomers substantially overlap the docked structure of combretastatin A-4, taken as reference ligand at the colchicine-tubulin binding site.
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Differences in outcome between twins and singletons born very preterm: results from a population-based European cohort.
Hum. Reprod.
PUBLISHED: 01-29-2010
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About 10% of twins are born before 32 weeks of gestation and very preterm birth rates are increasing. Preterm twins tend to have more favourable outcomes than singletons of the same gestational age, but fewer data are available for very preterm infants. This study aims to determine whether outcomes differ between very preterm twins and singletons.
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Changes in care and outcome of very preterm babies in the Parisian region between 1998 and 2003.
Arch. Dis. Child. Fetal Neonatal Ed.
PUBLISHED: 04-23-2009
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To assess evolution in the care and health of very preterm babies between 1998 and 2003 after implementation of a regionalisation policy in France.
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Effects of resveratrol analogs on cell cycle progression, cell cycle associated proteins and 5fluoro-uracil sensitivity in human derived colon cancer cells.
Int. J. Cancer
PUBLISHED: 04-01-2009
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Epidemiological studies suggested that trans-resveratrol, a wine grape component, could prevent malignant tumor development. This compound also demonstrated cytostatic and cytotoxic effects on tumor cells in vitro. To obtain trans-resveratrol derivatives with a better cellular uptake and enhanced antiproliferative effects, we synthesized a triacetate derivative as well as an oligomer, epsilon-viniferin and its acetylated form, epsilon-viniferin penta-acetate. We also obtained vineatrol, a wine grape shoot extract that associates several polyphenols that may act synergistically, including trans-resveratrol and epsilon-viniferin. We show here that resveratrol triacetate and vineatrol are as efficient as trans-resveratrol in inducing the accumulation of human colon cancer cells in early S phase of the cell cycle. This effect is associated with a nuclear redistribution of cyclin A and the formation of a cyclin A/cyclin-dependent kinase 2 complex whose kinase activity is increased. In contrast, epsilon-viniferin and its acetylated form do not demonstrate any significant activity on these cells when tested alone. Interestingly, resveratrol triacetate and vineatrol dramatically enhance 5-Fluoro-Uracil-mediated inhibition of colon cancer cell proliferation. Thus, acetylated derivatives of resveratrol have retained the cytostatic and cytotoxic activities of the parental molecule and thus deserve to be tested as chemosensitizers in animal models.
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A moderate red wine intake improves blood lipid parameters and erythrocytes membrane fluidity in post myocardial infarct patients.
Mol Nutr Food Res
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While the cardioprotective effect of moderate and regular wine consumption in primary prevention has been well documented, the goal of the present investigation was to explore the effect of wine intake on blood parameters (lipid, anti-oxidant capacity, and erythrocyte membrane potential and fluidity) in post myocardial infarct patients to evaluate perspectives in secondary prevention. A clinical intervention trial has been undertaken on a group of selected post myocardial infarct patients who gave written informed consent for participation in this study prior to enrolment. This two-week study has been conducted on hospitalized patients during a cardiac readaptation period. During this period, patients were submitted to a "Western prudent" diet (inspired by the Mediterranean diet) and two groups have been compared on a drawn basis: patients receiving red wine (250 mL daily) to patients receiving water. Physical, clinical, and blood parameters were evaluated on Days 1 and 14. The data show a positive effect of low wine consumption on blood parameters (decrease in total cholesterol and LDL; increase in erythrocyte membrane fluidity and antioxidant status). The results show that a moderate consumption of red wine even for a short period associated with a "Western prudent" diet improves various blood parameters in lipid and anti-oxidative status in patients with previous coronary ischemic accidents.
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Immunomodulation and anti-inflammatory roles of polyphenols as anticancer agents.
Anticancer Agents Med Chem
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Cancers are the largest cause of mortality and morbidity in industrialized countries. Several new concepts have emerged in relation to mechanisms that contribute to the regulation of carcinogenesis processes and associated inflammatory effects such as the modulation of innate immune cells and adaptive immune cells that could infiltrate the tumor. In the tumor microenvironment, there is a delicate balance between antitumor immunity and tumor-originated proinflammatory activity, which weaken antitumor immunity. Consequently; modulation of immune cells and inflammatory processes represent attractive targets for therapeutic intervention in malignant diseases with the goal to restore the sensitivity of cancer cells to chemotherapies and to overcome resistance to current cytotoxic therapies. Numerous studies have reported interesting properties of dietary polyphenols in anticancer strategies notably by their pleiotropic properties on cancer cells, immune cells and inflammation. This review is dedicated to the current knowledge of the mechanisms of polyphenols (resveratrol, curcumin, genistein and epigallocatechin) against cancers through a modulation of the immune system and the pro-inflammatory mediator production. We describe the effects of polyphenols on the adaptative and innate immune cells that could infiltrate the tumor. Reduction of chronic inflammation or its downstream consequences may represent a key mechanism in the fight of cancer development and polyphenols could reduce various pro-inflammatory substance productions through targeting signal transduction or through antioxidant effects. Lastly, we analyze key molecular links between inflammation and tumor progression through nuclear factors such as NF?B or microRNAs.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.