Bioinspired Microfibers with Embedded Perfusable Helical Channels

Materials with microchannels have attracted increasing attention due to their promising perfusability and biomimetic geometry. However, the fabrication of microfibers with more geometrically complex channels in the micro- or nanoscale remains a big challenge. Here, a novel method for generating scalable microfibers with consecutive embedded helical channels is presented using an easily made coaxial microfluidic device. The characteristics of the helical channel can be accurately controlled by simply adjusting the flow rate ratio of the fluids. The mechanism of the helix formation process is theorized with newly proposed heterogenerated rope-coil effect, which enhances the tunability of helical patterns and promotes the comprehension of this abnormal phenomenon. Based on this effect, microfibers with embedded Janus channels and even double helical channels are generated in situ by changing the design of the device. The uniqueness and potential applications of these tubular microfibers are also demonstrated by biomimetic supercoiling structures as well as the perfusable and permeable spiral vessel.

Novel microfibers with embedded helical channels are controllably fabricated in situ by a microfluidic strategy. Embedded double helical channels are fabricated with the guide of a proposed mechanism, which allows the construction of more complex 3D tissues in vitro. Successful perfusion and permeation in helical channels is also achieved as a demonstration of a spiral vessel.

http://ift.tt/2sTj0qf

Porphyrin Modified Trastuzumab Improves Efficacy of HER2 Targeted Photodynamic Therapy of Gastric Cancer

Abstract

Gastric cancer (GC) is the 3^rd deadliest cancer worldwide, due to limited treatment options and late diagnosis. Human epidermal growth factor receptor-2 (HER2) is overexpressed in ∼20% of GC cases and anti-HER2 antibody trastuzumab in combination with conventional chemotherapy, is recognized as standard therapy for HER2-positive metastatic GC. This strategy improves GC patients' survival by 2-3 months, however its optimal results in breast cancer indicate that GC survival may be improved. A new photoimmunoconjugate was developed by conjugating a porphyrin with trastuzumab (Trast:Porph) for targeted photodynamic therapy in HER2-positive GC. Using mass spectrometry analysis, the lysine residues in the trastuzumab structure most prone for porphyrin conjugation were mapped. The in vitro data demonstrates that Trast:Porph specifically binds to HER2-positive cells, accumulates intracellularly, co-localizes with lysosomal marker LAMP1, and induces massive HER2-positive cell death upon cellular irradiation. The high selectivity and cytotoxicity of Trast:Porph based photoimmunotherapy is confirmed in vivo in comparison with trastuzumab alone, using nude mice xenografted with a HER2-positive GC cell line. In the setting of human disease, these data suggest that repetitive cycles of Trast:Porph photoimmunotherapy may be used as an improved treatment strategy in HER2-positive GC patients. This article is protected by copyright. All rights reserved.

http://ift.tt/2tR0MTj

Large-scale genome-wide screening of circulating microRNAs in clear cell renal cell carcinoma reveals specific signatures in late-stage disease

Abstract

Circulating miRNAs have shown great promises as non-invasive diagnostic and predictive biomarkers in several solid tumors. While the miRNA profiles of renal tumors have been extensively explored, knowledge of their circulating counterparts is limited. Our study aimed to provide a large-scale genome-wide profiling of plasma circulating miRNA in clear-cell renal cell carcinoma (ccRCC).

Plasma samples from 94 ccRCC cases and 100 controls were screened for 754 circulating micro-RNAs (miRNA) by TaqMan arrays. Analyses including known risk factors for renal cancer, namely age, sex, hypertension, obesity, diabetes, tobacco smoking and alcohol consumption, highlighted that circulating miRNA profiles were tightly correlated with the stage of the disease. Advanced tumors, characterized as stage III and IV, were associated with specific miRNA signatures that significantly differ from both controls and earlier-stage ccRCC cases. Molecular pathway enrichment analyses of their gene targets showed high similarities with alterations observed in renal tumors. Plasma circulating levels of miR-150 were significantly associated with RCC-specific survival and could marginally improve the predictive accuracy of clinical parameters in our series, including age at diagnosis, sex and conventional staging.

In summary, our results suggest that circulating miRNAs may provide insights into renal cell carcinoma progression. This article is protected by copyright. All rights reserved.

http://ift.tt/2sTkf8T

High-Performance 2.6 V Aqueous Asymmetric Supercapacitors based on In Situ Formed Na0.5MnO2 Nanosheet Assembled Nanowall Arrays

The voltage limit for aqueous asymmetric supercapacitors is usually 2 V, which impedes further improvement in energy density. Here, high Na content Birnessite Na_0.5MnO₂ nanosheet assembled nanowall arrays are in situ formed on carbon cloth via electrochemical oxidation. It is interesting to find that the electrode potential window for Na_0.5MnO₂ nanowall arrays can be extended to 0–1.3 V (vs Ag/AgCl) with significantly increased specific capacitance up to 366 F g⁻¹. The extended potential window for the Na_0.5MnO₂ electrode provides the opportunity to further increase the cell voltage of aqueous asymmetric supercapacitors beyond 2 V. To construct the asymmetric supercapacitor, carbon-coated Fe₃O₄ nanorod arrays are synthesized as the anode and can stably work in a negative potential window of −1.3 to 0 V (vs Ag/AgCl). For the first time, a 2.6 V aqueous asymmetric supercapacitor is demonstrated by using Na_0.5MnO₂ nanowall arrays as the cathode and carbon-coated Fe₃O₄ nanorod arrays as the anode. In particular, the 2.6 V Na_0.5MnO₂//Fe₃O₄@C asymmetric supercapacitor exhibits a large energy density of up to 81 Wh kg⁻¹ as well as excellent rate capability and cycle performance, outperforming previously reported MnO₂-based supercapacitors. This work provides new opportunities for developing high-voltage aqueous asymmetric supercapacitors with further increased energy density.

Birnessite Na_0.5MnO₂ nanosheet assembled nanowall arrays are grown on carbon cloth via in situ electrochemical oxidation from spinel Mn₃O₄ nanowall arrays. By coupling with carbon-coated Fe₃O₄ nanorod arrays as the anode, a 2.6 V aqueous asymmetric supercapacitor is successfully developed. It exhibits a high energy density of 81 Wh kg⁻¹ as well as excellent power capability and cycle performance.

http://ift.tt/2tQRZkc

Van der Waals Epitaxial Growth of Atomic Layered HfS2 Crystals for Ultrasensitive Near-Infrared Phototransistors

As a member of the group IVB transition metal dichalcogenides (TMDs) family, hafnium disulfide (HfS₂) is recently predicted to exhibit higher carrier mobility and higher tunneling current density than group VIB (Mo and W) TMDs. However, the synthesis of high-quality HfS₂ crystals, sparsely reported, has greatly hindered the development of this new field. Here, a facile strategy for controlled synthesis of high-quality atomic layered HfS₂ crystals by van der Waals epitaxy is reported. Density functional theory calculations are applied to elucidate the systematic epitaxial growth process of the S-edge and Hf-edge. Impressively, the HfS₂ back-gate field-effect transistors display a competitive mobility of 7.6 cm² V⁻¹ s⁻¹ and an ultrahigh on/off ratio exceeding 10⁸. Meanwhile, ultrasensitive near-infrared phototransistors based on the HfS₂ crystals (indirect bandgap ≈1.45 eV) exhibit an ultrahigh responsivity exceeding 3.08 × 10⁵ A W⁻¹, which is 10⁹-fold higher than 9 × 10⁻⁵ A W⁻¹ obtained from the multilayer MoS₂ in near-infrared photodetection. Moreover, an ultrahigh photogain exceeding 4.72 × 10⁵ and an ultrahigh detectivity exceeding 4.01 × 10¹² Jones, superior to the vast majority of the reported 2D-materials-based phototransistors, imply a great promise in TMD-based 2D electronic and optoelectronic applications.

A facile strategy for the synthesis of high-quality monolayer HfS₂ crystals by van der Waals epitaxy is reported. Ultrasensitive near-infrared phototransistors based on the HfS₂ crystals exhibit an ultrahigh responsivity 3.08 × 10⁵ A W⁻¹, and an ultrahigh detectivity exceeding 4.01 × 10¹² Jones, superior to most 2D materials-based phototransistors.

http://ift.tt/2sT8Aa6

Amorphous Metallic NiFeP: A Conductive Bulk Material Achieving High Activity for Oxygen Evolution Reaction in Both Alkaline and Acidic Media

The intrinsic catalytic activity at 10 mA cm⁻² for oxygen evolution reaction (OER) is currently working out at overpotentials higher than 320 mV. A highly efficient electrocatalyst should possess both active sites and high conductivity; however, the loading of powder catalysts on electrodes may often suffer from the large resistance between catalysts and current collectors. This work reports a class of bulk amorphous NiFeP materials with metallic bonds from the viewpoint of electrode design. The materials reported here perfectly combine high macroscopic conductivity with surface active sites, and can be directly used as the electrodes with active sites toward high OER activity in both alkaline and acidic electrolytes. Specifically, a low overpotential of 219 mV is achieved at the geometric current density 10 mA cm⁻² in an alkaline electrolyte, with the Tafel slope of 32 mV dec⁻¹ and intrinsic overpotential of 280 mV. Meanwhile, an overpotential of 540 mV at 10 mA cm⁻² is attained in an acidic electrolyte and stable for over 30 h, which is the best OER performance in both alkaline and acidic media. This work provides a different angle for the design of high-performance OER electrocatalysts and facilitates the device applications of electrocatalysts.

A class of bulk amorphous NiFeP materials that perfectly combines high macroscopic conductivity with surface active sites is developed toward high activity for oxygen evolution reaction in both alkaline and acidic electrolytes. The synergistic effect of coordinatively unsaturated Ni, Fe, and P constitutes the highly active sites, while the high macroscopic conductivity facilitates the charge transfer from catalyst surface to current collector.

http://ift.tt/2tQEukF

Spatiotemporally Controllable Peptide-Based Nanoassembly in Single Living Cells for a Biological Self-Portrait

Simultaneous precise localization and activity evaluation of a biomolecule in a single living cell is through an enzyme-specific signal-amplification process, which involves the localized, site-specific self-assembly, and activation of a presignaling molecule. The inactive presignaling tetraphenylethylene (TPE)-peptide derivative, TPE-YpYY, is nondetectable and highly biocompatible and these small molecules rapidly diffuse into living cells. Upon safely arriving at an active site, and accessing the catalytic pocket of an enzyme, TPE-YpYY immediately and quantitatively accumulates in situ in response to enzymatic activity, forms an enzyme anchor TPE-YYY nanoassembly, displays aggregation-induced emission behavior, and finally lights up the active enzyme, indicating its activity, and allowing its status in living cells to be tracked. This simple and direct self-portrait method can be used to monitor dynamic self-assembly processes in individual living cells and may provide new insights that reveal undiscovered biological processes and that aid in developing biomedical hybrid devices. In the future, this strategy of molecular design can be further expanded to the noninvasive investigation of other bioactive molecules, thus facilitating quantitative imaging.

When activated by an enzyme, a synthesized cell-permeable probe forms biomolecule-anchored complexes and thus simultaneously evaluates the real-time location and bioactivity of the enzyme in single live cells. This simple and direct method can be used to monitor single-cell dynamic self-assembly processes in vitro and in vivo, which may provide new insights into previously undiscovered biological processes.

http://ift.tt/2sTdrIj

Fully-Inorganic Trihalide Perovskite Nanocrystals: A New Research Frontier of Optoelectronic Materials

All-inorganic trihalide perovskite nanocrystals (NCs) are emerging as a new class of superstar semiconductors with excellent optoelectronic properties and great potential for a broad range of applications in lighting, lasing, photon detection, and photovoltaics. This article provides an up-to-date review on the developments of fully-inorganic trihalide perovskite NCs by emphasizing their controllable solution fabrication strategies, structural phase transformation, tunable optoelectronic properties, stability, as well as their photovoltaic and optoelectronic applications. Among the properties to be surveyed, particular focus is on the size-, shape-, and composition-dependent photoluminescence properties. Finally, by identifying new challenges, suggestions are provided for further research and potential development of this area.

The fundamental aspects of fully-inorganic trihalide perovskite nanocrystals as a new class of superstar semiconductors are briefly reviewed. In addition to excellent optoelectronic properties and broad range of applications, the controllable fabrication strategies, structure transformation and stability are comprehensively discussed. Some sugestions for improving the nanomaterials and device performance and potential development of this area in the near future are also proposed.

http://ift.tt/2sWp95E

Epitaxial Lift-Off of Centimeter-Scaled Spinel Ferrite Oxide Thin Films for Flexible Electronics

Mechanical flexibility of electronic devices has attracted much attention from research due to the great demand in practical applications and rich commercial value. Integration of functional oxide materials in flexible polymer materials has proven an effective way to achieve flexibility of functional electronic devices. However, the chemical and mechanical incompatibilities at the interfaces of dissimilar materials make it still a big challenge to synthesize high-quality single-crystalline oxide thin film directly on flexible polymer substrates. This study reports an improved method that is employed to successfully transfer a centimeter-scaled single-crystalline LiFe₅O₈ thin film on polyimide substrate. Structural characterizations show that the transferred films have essentially no difference in comparison with the as-grown films with respect to the microstructure. In particular, the transferred LiFe₅O₈ films exhibit excellent magnetic properties under various mechanical bending statuses and show excellent fatigue properties during the bending cycle tests. These results demonstrate that the improved transfer method provides an effective way to compose single-crystalline functional oxide thin films onto flexible substrates for applications in flexible and wearable electronics.

Flexible centimeter-scaled single-crystalline spinel ferrite oxide thin films are transferred onto plastic substrates using a simple method. The transferred thin films exhibit not only excellent fatigue property but also stable magnetic properties even under various bend status. The results provide evidence for a practical way to transfer target single-crystalline functional oxide thin films onto flexible substrates for applications in flexible and wearable electronics.

http://ift.tt/2tw4C4X

A Retina-Like Dual Band Organic Photosensor Array for Filter-Free Near-Infrared-to-Memory Operations

Human eyes use retina photoreceptor cells to absorb and distinguish photons from different wavelengths to construct an image. Mimicry of such a process and extension of its spectral response into the near-infrared (NIR) is indispensable for night surveillance, retinal prosthetics, and medical imaging applications. Currently, NIR organic photosensors demand optical filters to reduce visible interference, thus making filter-free and anti-visible NIR imaging a challenging task. To solve this limitation, a filter-free and conformal, retina-inspired NIR organic photosensor is presented. Featuring an integration of photosensing and floating-gate memory modules, the device possesses an acute color distinguishing capability. In general, the retina-like photosensor transduces NIR (850 nm) into nonvolatile memory and acts as a dynamic photoswitch under green light (550 nm). In doing this, a filter-free but color-distinguishing photosensor is demonstrated that selectively converts NIR optical signals into nonvolatile memory.

Using organic dye materials—both molecular and polymeric—a retina-like, filter-free photosensor with a near infrared (NIR) signal to nonvolatile memory is realized. The device features an integration of photosensing elements and floating-gate memories, and is capable of distinguishing 550-nm light and 850-nm light by a bimodal operation. This result provides innovation for intelligent photosensors with acute wavelength selectivity.

http://ift.tt/2sWrfT5

Bilayer PbS Quantum Dots for High-Performance Photodetectors

Due to their wide tunable bandgaps, high absorption coefficients, easy solution processabilities, and high stabilities in air, lead sulfide (PbS) quantum dots (QDs) are increasingly regarded as promising material candidates for next-generation light, low-cost, and flexible photodetectors. Current single-layer PbS-QD photodetectors suffer from shortcomings of large dark currents, low on–off ratios, and slow light responses. Integration with metal nanoparticles, organics, and high-conducting graphene/nanotube to form hybrid PbS-QD devices are proved capable of enhancing photoresponsivity; but these approaches always bring in other problems that can severely hamper the improvement of the overall device performance. To overcome the hurdles current single-layer and hybrid PbS-QD photodetectors face, here a bilayer QD-only device is designed, which can be integrated on flexible polyimide substrate and significantly outperforms the conventional single-layer devices in response speed, detectivity, linear dynamic range, and signal-to-noise ratio, along with comparable responsivity. The results which are obtained here should be of great values in studying and designing advanced QD-based photodetectors for applications in future flexible optoelectronics.

A bilayer lead-sulfide-quantum-dot-only photodetector is designed, which significantly outperforms conventional single-layer devices in response speed, detectivity, linear dynamic range, and signal-to-noise ratio. Careful investigation finds that junction-controlled carrier separation and recombination is responsible for the superiority of the bilayer device. The bilayer devices also signal their great potential in future flexible optoelectronics.

http://ift.tt/2tw9RkW

High-Energy/Power and Low-Temperature Cathode for Sodium-Ion Batteries: In Situ XRD Study and Superior Full-Cell Performance

Sodium-ion batteries (SIBs) are still confronted with several major challenges, including low energy and power densities, short-term cycle life, and poor low-temperature performance, which severely hinder their practical applications. Here, a high-voltage cathode composed of Na₃V₂(PO₄)₂O₂F nano-tetraprisms (NVPF-NTP) is proposed to enhance the energy density of SIBs. The prepared NVPF-NTP exhibits two high working plateaux at about 4.01 and 3.60 V versus the Na⁺/Na with a specific capacity of 127.8 mA h g⁻¹. The energy density of NVPF-NTP reaches up to 486 W h kg⁻¹, which is higher than the majority of other cathode materials previously reported for SIBs. Moreover, due to the low strain (≈2.56% volumetric variation) and superior Na transport kinetics in Na intercalation/extraction processes, as demonstrated by in situ X-ray diffraction, galvanostatic intermittent titration technique, and cyclic voltammetry at varied scan rates, the NVPF-NTP shows long-term cycle life, superior low-temperature performance, and outstanding high-rate capabilities. The comparison of Ragone plots further discloses that NVPF-NTP presents the best power performance among the state-of-the-art cathode materials for SIBs. More importantly, when coupled with an Sb-based anode, the fabricated sodium-ion full-cells also exhibit excellent rate and cycling performances, thus providing a preview of their practical application.

A high-voltage sodium-super-ion-conductor-type cathode significantly enhances the energy density of sodium-ion batteries. Its low-strain crystal lattice during the successive (de-)sodiation and superior Na transport kinetics promise high-rate capabilities, long-term cycle life, superior low-temperature performance, and excellent full-cell performance, providing a preview of their practical applications.

http://ift.tt/2sXOv2t

In defense of Bacillus thuringiensis , the safest and most successful microbial insecticide available to humanity – a response to EFSA

Abstract

The Bacillus cereus group contains vertebrate pathogens such as Bacillus anthracis and Bacillus cereus and the invertebrate pathogen Bacillus thuringiensis. Microbial biopesticides based on B. thuringiensis (Bt) are widely recognized as being among the safest and least environmentally damaging insecticidal products available. Nevertheless, a recent food poisoning incident prompted a European Food Safety Authority review which argued that B. thuringiensis poses a health risk equivalent to B. cereus, a causative agent of diarrhoea. However, a critical examination of available data, and this latest incident, provide no solid evidence that B. thuringiensis causes diarrhoea. Although relatively high levels of B. cereus-like spores can occur in foods, genotyping demonstrates that these are predominantly naturally-occurring strains rather than biopesticides. Moreover, MLST genotyping of > 2000 isolates show that biopesticide genotypes have never been isolated from any clinical infection. MLST data demonstrate that Bacillus cereus group is heterogeneous and formed of distinct clades with substantial differences in biology, ecology and host association. The group posing the greatest risk (the anthracis clade) is distantly related to the clade containing all biopesticides. These recent data support the long-held view that B. thuringiensis, and especially the strains used in Bt biopesticides, are very safe for humans.

http://ift.tt/2sSXpOw

Temporal variation of the microbiome is dependent on body region in a wild mammal ( Tamiasciurus hudsonicus)

Abstract

Microbial communities are increasingly being recognized as important to host health in wild mammals, but how these communities are characterized can have important consequences on the results of these studies. Previous research has explored temporal variation in microbial communities in humans and lab mammals, but few have investigated how microbiomes fluctuate in wild populations and none have examined the temporal dynamics of these fluctuations in different body regions on a wild mammal. Using Illumina MiSeq sequencing of the V3-V4 16S rRNA gene regions, we characterized the buccal and gut microbiomes of wild North American red squirrels, Tamiasciurus hudsonicus, to measure changes in these two microbiomes over short (< 2 weeks), medium (2–4 weeks) and long (> 1 month) term sampling periods. While we observed short and medium temporal stability in the buccal microbiome, the gut microbiome varied between medium and long term sampling periods. There was no evidence of intra-individual correlations between buccal and gut microbiome change, suggesting that temporal stability is dependent on the body region and factors affecting microbial stability may be specific to body sites. From these findings, we urge researchers to be cautious in interpreting results from single temporal sampling periods when quantifying characteristic microbiomes in wild mammals.

http://ift.tt/2tQLazj

Soil prokaryotic communities in Chernobyl waste disposal trench T22 are modulated by organic matter and radionuclide contamination

Abstract

After the Chernobyl nuclear power plant accident in 1986, contaminated soils, vegetation from the Red Forest, and other radioactive debris were buried within trenches. In this area, trench T22 has long been a pilot site for the study of radionuclide migration in soil. Here, we used 454 pyrosequencing of 16S rRNA genes to obtain a comprehensive view of the bacterial and archaeal diversity in soils collected inside and in the vicinity of the trench T22 and to investigate the impact of radioactive waste disposal on prokaryotic communities. A remarkably high abundance of Chloroflexi and AD3 was detected in all soil samples from this area. Our statistical analysis revealed profound changes in community composition at the phylum and OTUs levels and higher diversity in the trench soils as compared to the outside. Our results demonstrate that the total absorbed dose rate by cell and, to a lesser extent the organic matter content of the trench, are the principal variables influencing prokaryotic assemblages. We identified specific phylotypes affiliated to the phyla Crenarchaeota, Acidobacteria, AD3, Chloroflexi, Proteobacteria, Verrucomicrobia and WPS-2, which were unique for the trench soils.

http://ift.tt/2sT9sv0

Genomic Characterization of Two Novel SAR11 Isolates From the Red Sea, Including the First Strain of the SAR11 Ib clade

Abstract

The SAR11 clade (Pelagibacterales) is a diverse group that forms a monophyletic clade within the Alphaproteobacteria, and constitutes up to one third of all prokaryotic cells in the photic zone of most oceans. Pelagibacterales are very abundant in the warm and highly saline surface waters of the Red Sea, raising the question of adaptive traits of SAR11 populations in this water body and warmer oceans through the world. In this study, two pure cultures were successfully obtained from surface waters on the Red Sea, one isolate of subgroup Ia and one of the previously uncultured SAR11 Ib lineage. The novel genomes were very similar to each other and to genomes of isolates of SAR11 subgroup Ia (Ia pan-genome), both in terms of gene content and synteny. Among the genes that were not present in the Ia pan-genome, 108 (RS39, Ia) and 151 genes (RS40, Ib) were strain-specific. Detailed analyses showed that only 51 (RS39, Ia) and 55 (RS40, Ib) of these strain-specific genes had not reported before on genome fragments of Pelagibacterales. Further analyses revealed the potential production of phosphonates by some SAR11 members and possible adaptations for oligotrophic life, including pentose sugar utilization and adhesion to marine particulate matter.

http://ift.tt/2tQOhr2

Mapping the Allosteric Sites of the A2A Adenosine Receptor

Abstract

The A_2A adenosine receptor (A_2AAR) is a G protein-coupled receptor that is pharmacologically targeted for the treatment of inflammation, sepsis, cancer, neuro-degeneration, and Parkinson's disease. Recently, we applied long-timescale molecular dynamics simulations on two ligand-free receptor conformations, starting from the agonist-bound (PDB ID:3QAK) and antagonist-bound (PDB ID:3EML) X-ray structures. This analysis revealed four distinct conformers of the A_2AAR: the active, intermediate 1, intermediate 2, and inactive. In this study, we apply the fragment-based mapping algorithm, FTMap, on these receptor conformations to uncover five non-orthosteric sites on the A_2AAR. Two sites that are identified in the active conformation are located in the intracellular region of the transmembrane helices (TM) 3/TM4 and the G protein-binding site in the intracellular region between TM2/TM3/TM6/TM7. Three sites are identified in the intermediate 1 and intermediate 2 conformations, annexing a site in the lipid interface of TM5/TM6. Five sites are identified in the inactive conformation, comprising of a site in the intracellular region of TM1/TM7, and in the extracellular region of TM3/TM4 of the A_2AAR. We postulate that these sites on the A_2AAR be screened for allosteric modulators for the treatment of inflammatory and neurological diseases.

This article is protected by copyright. All rights reserved.

We uncover five non-ortnosteric sites on the A_2A adenosine receptor that can be screened for allosteric modulators for the treatment of inflammatory and neurological diseases. Site one is in the intracellular region of the transmembrane helices (TM) 3/TM4, and site two is the G protein-binding site between TM2/TM3/TM6/TM7. Site three is on the lipid interface of TM5/TM6, site four is in the intracelluar region of TM1/TM7, and site five is in the extracellular region of TM3/TM4.

http://ift.tt/2st5jxw

Design, synthesis, and biological evaluation of a new class of benzo[b]furan derivatives as antiproliferative agents, with in silico predicted antitubulin activity

Abstract

A new series of 3-benzoylamino-5-(1H-imidazol-4-yl)methylaminobenzo[b]furans were synthesized and screened as antitumor agents. As a general trend, tested compounds showed concentration-dependent antiproliferative activity against HeLa and MCF-7 cancer cell lines, exhibiting GI₅₀ values in the low micromolar range. In most cases, insertion of a methyl substituent on the imidazole moiety improved the antiproliferative activity. Therefore, methyl-imidazolyl-benzo[b]furans compounds were tested in cell cycle perturbation experiments, producing cell cycle arrest with proapoptotic effects. Their core similarity to known colchicine binding site binders led us to further study the structure features as antitubulin agents by in silico protocols.

This article is protected by copyright. All rights reserved.

A new series of 3-benzoylamino-5-(1H-imidazol-4-yl)methylaminobenzo[b]furans were synthesized and screened as antitumor agents. The MTT test (HeLa and MCF-7) underlined a significant growth inhibition effect of the derivatives 7a-f. Compounds 7b-d,f, tested in cell cycle perturbation experiments on HeLa cells produced a cell cycle arrest in G2/M phase. In addition, the structure similarity of these benzo[b]furans with known colchicine binding sites binders led us to investigate their potent interference with the microtubule system by computational analysis as a support of the observed biological effects.

http://ift.tt/2rXKLJO

The dietary intake of flavonoids reduces the risk of developing certain types of cancers.Anticancer and preventive effects against prostate,colorectal,breast,thyroid,lung,and ovarian cancers,Flavonoids include the following subfamilies: flavones, flavanols, isoflavones, flavonols, flavanones, and flavanonols, which differ in their ring substituents and extent of saturation.............................................................................................................................Silymarin, genistein, quercetin, daidzein, luteolin, kaempferol, apigenin, and epigallocatechin 3-gallate.Their chemopreventive efficacy is mediated by inhibiting the development of new cancer cells;preventing carcinogens from reaching their activation sites; and decreasing the toxicity of certain compounds by inhibiting their metabolism.The molecular mechanisms by which flavonoids produce their anticancer and preventive effects include (1) induction of apoptosis ; (2) cell cycle arrest at G1

http://orl-agios.blogspot.com/2017/06/the-preclinical-anticancer-effect-of.html

Flavonoids present in foods were considered non-absorbable because they are bound to sugars as beta-glycosides. However, we found that human absorption of the quercetin glycosides from onions (52%) is far better than that of the pure aglycone (24%). Flavonol glycosides might contribute to the antioxidant defences of blood. Dietary flavonols and flavones probably do not explain the cancer-protective effect of vegetables and fruits; a protective effect against cardiovascular disease is not conclusive.Flavonoids and their polymers constitute a large class of food constituents, many of which alter metabolic processes and have a positive impact on health. Flavonoids are a subclass of polyphenols. They generally consist of two aromatic rings, each containing at least one hydroxyl, which are connected through a three-carbon "bridge" and become part of a six-member heterocyclic ring. The flavonoids are further divided into subclasses based on the connection of an aromatic ring to the heterocyclic ring, as well as the oxidation state and functional groups of the heterocyclic ring. Within each subclass, individual compounds are characterized by specific hydroxylation and conjugation patterns. Many flavonoids in foods also occur as large molecules (tannins). These include condensed tannins (proanthocyanidins), derived tannins and hydrolysable tannins. For proanthocyanidins, three subclasses (15 characterized) have been identified in foods. Monomers are connected through specific carbon-carbon and ether linkages to form polymers. Derived tannins are formed during food handling and processing, and found primarily in black and oolong teas. Flavonoids are widely distributed in nature, albeit not uniformly. As a result, specific groups of foods are often rich sources of one or more subclasses of these polyphenols. The polyphenolic structure of flavonoids and tannins renders them quite sensitive to oxidative enzymes and cooking conditions. Scientists in several countries have estimated intakes of a few subclasses of flavonoids from limited food composition databases. These observations suggest large differences in consumption, due in part to cultural and food preferences among populations of each country.

Flavonoids (specifically flavanoids such as the catechins) are "the most common group of polyphenoliccompounds in the human diet and are found ubiquitously in plants".^[6] Flavonols, the original bioflavonoids such as quercetin, are also found ubiquitously, but in lesser quantities. The widespread distribution of flavonoids, their variety and their relatively low toxicity compared to other active plant compounds (for instance alkaloids) mean that many animals, including humans, ingest significant quantities in their diet. Foods with a high flavonoid content include parsley,^[7] onions,^[7] blueberries and other berries,^[7] black tea,^[7] green tea and oolong tea,^[7] bananas, all citrus fruits, Ginkgo biloba, red wine, sea-buckthorns, anddark chocolate (with a cocoa content of 70% or greater). Further information on dietary sources of flavonoids can be obtained from the US Department of Agriculture flavonoid database.^[7]

Flavonoid

From Wikipedia, the free encyclopedia

Molecular structure of theflavone backbone (2-phenyl-1,4-benzopyrone)

Isoflavan structure

Neoflavonoids structure

Flavonoids (or bioflavonoids) (from the Latin word flavus meaning yellow, their color in nature) are a class ofplant and fungus secondary metabolites.

Chemically, flavonoids have the general structure of a 15-carbon skeleton, which consists of two phenyl rings (A and B) and heterocyclic ring (C). This carbon structure can be abbreviated C6-C3-C6. According to the IUPACnomenclature,^[1][2] they can be classified into:

• flavonoids or bioflavonoids
• isoflavonoids, derived from 3-phenylchromen-4-one (3-phenyl-1,4-benzopyrone) structure
• neoflavonoids, derived from 4-phenylcoumarine (4-phenyl-1,2-benzopyrone) structure

The three flavonoid classes above are all ketone-containing compounds, and as such, are anthoxanthins (flavonesand flavonols). This class was the first to be termed bioflavonoids. The terms flavonoid and bioflavonoid have also been more loosely used to describe non-ketone polyhydroxy polyphenol compounds which are more specifically termed flavanoids. The three cycle or heterocycles in the flavonoid backbone are generally called ring A, B and C. Ring A usually shows a phloroglucinol substitution pattern.

Contents

  [hide] 

• 1Biosynthesis
• 2Functions of flavonoids in plants
• 3Subgroups
  • 3.1Anthoxanthins
  • 3.2Flavanones
  • 3.3Flavanonols
  • 3.4Flavans
  • 3.5Anthocyanidins
• 4Isoflavonoids
• 5Dietary sources
  • 5.1Parsley
  • 5.2Blueberries
  • 5.3Black tea
  • 5.4Citrus
  • 5.5Wine
  • 5.6Cocoa
  • 5.7Peanut
• 6Dietary intake
• 7Research
  • 7.1In vitro
  • 7.2Antioxidant
  • 7.3Inflammation
  • 7.4Cancer
  • 7.5Cardiovascular diseases
  • 7.6Antibacterial
• 8Synthesis, detection, quantification, and semi-synthetic alterations
  • 8.1Color spectrum
  • 8.2Availability through microorganisms
  • 8.3Tests for detection
  • 8.4Quantification
  • 8.5Semi-synthetic alterations
• 9See also
• 10References
• 11Further reading
• 12External links
  • 12.1Databases

Biosynthesis[edit]

Main article: Flavonoid biosynthesis

Functions of flavonoids in plants[edit]

Flavonoids are widely distributed in plants, fulfilling many functions. Flavonoids are the most important plant pigments for flower coloration, producing yellow or red/blue pigmentation in petals designed to attract pollinator animals. In higher plants, flavonoids are involved in UV filtration, symbiotic nitrogen fixation and floral pigmentation. They may also act as chemical messengers, physiological regulators, and cell cycle inhibitors. Flavonoids secreted by the root of their host plant help Rhizobia in the infection stage of their symbiotic relationship with legumes like peas, beans, clover, and soy. Rhizobia living in soil are able to sense the flavonoids and this triggers the secretion of Nod factors, which in turn are recognized by the host plant and can lead to root hair deformation and several cellular responses such as ion fluxes and the formation of a root nodule. In addition, some flavonoids have inhibitory activity against organisms that cause plant diseases, e.g. Fusarium oxysporum.^[3]

Subgroups[edit]

Over 5000 naturally occurring flavonoids have been characterized from various plants. They have been classified according to their chemical structure, and are usually subdivided into the following subgroups (for further reading see^[4]):

Anthoxanthins[edit]

Anthoxanthins are divided into two groups:^[5]

Group	Skeleton				Examples
	Description	Functional groups		Structural formula
		3-hydroxyl	2,3-dihydro
Flavone	2-phenylchromen-4-one	✗	✗		Luteolin, Apigenin, Tangeritin
Flavonol or 3-hydroxyflavone	3-hydroxy-2-phenylchromen-4-one	✓	✗		Quercetin, Kaempferol, Myricetin, Fisetin, Galangin,Isorhamnetin, Pachypodol, Rhamnazin,Pyranoflavonols, Furanoflavonols,

Flavanones[edit]

Flavanones

Group	Skeleton				Examples
	Description	Functional groups		Structural formula
		3-hydroxyl	2,3-dihydro
Flavanone	2,3-dihydro-2-phenylchromen-4-one	✗	✓		Hesperetin, Naringenin, Eriodictyol,Homoeriodictyol

Flavanonols[edit]

Flavanonols

Group	Skeleton				Examples
	Description	Functional groups		Structural formula
		3-hydroxyl	2,3-dihydro
Flavanonol or 3-Hydroxyflavanone or 2,3-dihydroflavonol	3-hydroxy-2,3-dihydro-2-phenylchromen-4-one	✓	✓		Taxifolin (orDihydroquercetin),Dihydrokaempferol

Flavans[edit]

Flavan structure

Include flavan-3-ols (flavanols), flavan-4-ols and flavan-3,4-diols.

Skeleton	Name
	Flavan-3-ol (flavanol)
	Flavan-4-ol
	Flavan-3,4-diol (leucoanthocyanidin)

• Flavan-3-ols (flavanols)
  • Flavan-3-ols use the 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton

  Examples: Catechin (C), Gallocatechin (GC), Catechin 3-gallate (Cg), Gallocatechin 3-gallate (GCg), Epicatechins (Epicatechin (EC)),Epigallocatechin (EGC), Epicatechin 3-gallate (ECg), Epigallocatechin 3-gallate (EGCg)

  • Theaflavin

  Examples: Theaflavin-3-gallate, Theaflavin-3'-gallate, Theaflavin-3,3'-digallate

  • Thearubigin
  • Proanthocyanidins are dimers, trimers, oligomers, or polymers of the flavanols

Anthocyanidins[edit]

Flavylium skeleton of anthocyanidins

• Anthocyanidins

  Anthocyanidins are the aglycones of anthocyanins; they use the flavylium (2-phenylchromenylium) ion skeleton

  Examples: Cyanidin, Delphinidin, Malvidin, Pelargonidin, Peonidin, Petunidin

Isoflavonoids[edit]

• Isoflavonoids
  • Isoflavones use the 3-phenylchromen-4-one skeleton (with no hydroxyl group substitution on carbon at position 2)

  Examples: Genistein, Daidzein, Glycitein

  • Isoflavanes
  • Isoflavandiols
  • Isoflavenes
  • Coumestans
  • Pterocarpans

Dietary sources[edit]

Parsley is a source of flavones.

Blueberries are a source of dietary anthocyanidins.

A variety of flavonoids are found incitrus fruits, including grapefruit.

Flavonoids (specifically flavanoids such as the catechins) are "the most common group of polyphenoliccompounds in the human diet and are found ubiquitously in plants".^[6] Flavonols, the original bioflavonoids such as quercetin, are also found ubiquitously, but in lesser quantities. The widespread distribution of flavonoids, their variety and their relatively low toxicity compared to other active plant compounds (for instance alkaloids) mean that many animals, including humans, ingest significant quantities in their diet. Foods with a high flavonoid content include parsley,^[7] onions,^[7] blueberries and other berries,^[7] black tea,^[7] green tea and oolong tea,^[7] bananas, all citrus fruits, Ginkgo biloba, red wine, sea-buckthorns, anddark chocolate (with a cocoa content of 70% or greater). Further information on dietary sources of flavonoids can be obtained from the US Department of Agriculture flavonoid database.^[7]

Parsley[edit]

Parsley, both fresh and dried, contains flavones.^[7]

Blueberries[edit]

Blueberries are a dietary source of anthocyanidins.^[7][8]

Black tea[edit]

Black tea is a rich source of dietary flavan-3-ols.^[7]

Citrus[edit]

The citrus flavonoids include hesperidin (a glycoside of the flavanone hesperetin), quercitrin, rutin (twoglycosides of the flavonol quercetin), and the flavone tangeritin.

Wine[edit]

Main article: Polyphenols in wine

Cocoa[edit]

Main article: Health effects of chocolate

Flavonoids exist naturally in cocoa, but because they can be bitter, they are often removed from chocolate, even dark chocolate.^[9] Although flavonoids are present in milk chocolate, milk may interfere with their absorption;^[10][11] however this conclusion has been questioned.^[12]

Peanut[edit]

Peanut (red) skin contains significant polyphenol content, including flavonoids.^[13][14]

Food source	Flavones	Flavonols	Flavanones
Red onion	0	4 - 100	0
Parsley, fresh	24 - 634	8 - 10	0
Thyme, fresh	56	0	0
Lemon juice, fresh	0	0 - 2	2 - 175

^[15]

Dietary intake[edit]

Mean flavonoid intake in mg/d per country, the pie charts show the relative contribution of different types of flavonoids.^[16]

Food composition data for flavonoids were provided by the USDA database on flavonoids.^[7] In the United States NHANES survey, mean flavonoid intake was 190 mg/d in adults, with flavan-3-ols as the main contributor.^[17] In the European Union, based on data from EFSA, mean flavonoid intake was 140 mg/d, although there were considerable differences between individual countries.^[16]

Data is based on mean flavonoid intake of all countries included in the 2011 EFSA Comprehensive European Food Consumption Database.^[16]

The main type of flavonoids consumed in the EU and USA were flavan-3-ols, mainly from tea, while intake of other flavonoids was considerably lower.^[16][17]

Research[edit]

Though there is ongoing research into the potential health benefits of individual flavonoids, neither theFood and Drug Administration (FDA) nor the European Food Safety Authority (EFSA) has approved any health claim for flavonoids or approved any flavonoids as pharmaceutical drugs.^[18][19][20] Moreover, several companies have been cautioned by the FDA over misleading health claims.^{[21][22][23][24]}

In vitro[edit]

Flavonoids have been shown to have a wide range of biological and pharmacological activities in in vitrostudies. Examples include anti-allergic,^[25] anti-inflammatory,^[25][26] antioxidant,^[26] anti-microbial(antibacterial,^[27][28] antifungal,^[29][30] and antiviral^[29][30]), anti-cancer,^[26][31] and anti-diarrheal activities.^[32]Flavonoids have also been shown to inhibit topoisomerase enzymes^[33][34] and to induce DNA mutations in the mixed-lineage leukemia (MLL) gene in in vitro studies.^[35] However, in most of the above cases no follow up in vivo or clinical research has been performed, leaving it impossible to say if these activities have any beneficial or detrimental effect on human health. Biological and pharmacological activities which have been investigated in greater depth are described below.

Antioxidant[edit]

Research at the Linus Pauling Institute and the European Food Safety Authority shows that flavonoids are poorly absorbed in the human body (less than 5%), with most of what is absorbed being quickly metabolized and excreted.^[20][36][37] These findings suggest that flavonoids have negligible systemic antioxidant activity, and that the increase in antioxidant capacity of blood seen after consumption of flavonoid-rich foods is not caused directly by flavonoids, but is due to production of uric acid resulting from flavonoid depolymerizationand excretion.^[38]

Inflammation[edit]

Inflammation has been implicated as a possible origin of numerous local and systemic diseases, such ascancer,^[39] cardiovascular disorders,^[40] diabetes mellitus,^[41] and celiac disease.^[42]

Preliminary studies indicate that flavonoids may affect anti-inflammatory mechanisms via their ability to inhibit reactive oxygen or nitrogen compounds.^[43] Flavonoids have also been proposed to inhibit the pro-inflammatory activity of enzymes involved in free radical production, such as cyclooxygenase, lipoxygenaseor inducible nitric oxide synthase,^[43][44] and to modify intracellular signaling pathways in immune cells,^[43] or in brain cells after a stroke.^[45]

Procyanidins, a class of flavonoids, have been shown in preliminary research to have anti-inflammatory mechanisms including modulation of thearachidonic acid pathway, inhibition of gene transcription, expression and activity of inflammatory enzymes, as well as secretion of anti-inflammatory mediators.^[46]

Cancer[edit]

Clinical studies investigating the relationship between flavonoid consumption and cancer prevention/development are conflicting for most types of cancer, probably because most studies are retrospective in design and use a small sample size.^[47] Two apparent exceptions are gastric carcinomaand smoking-related cancers. Dietary flavonoid intake is associated with reduced gastric carcinoma risk in women,^[48] and reduced aerodigestive tract cancer risk in smokers.^[49]

Cardiovascular diseases[edit]

Among the most intensively studied of general human disorders possibly affected by dietary flavonoids, preliminary cardiovascular diseaseresearch has revealed the following mechanisms under investigation in patients or normal subjects:^{[50][51][52][53][54]}

• inhibit coagulation, thrombus formation or platelet aggregation
• reduce risk of atherosclerosis
• reduce arterial blood pressure and risk of hypertension
• reduce oxidative stress and related signaling pathways in blood vessel cells
• modify vascular inflammatory mechanisms
• improve endothelial and capillary function
• modify blood lipid levels
• regulate carbohydrate and glucose metabolism
• modify mechanisms of aging

Listed on the clinical trial registry of the US National Institutes of Health (July 2016) are 48 human studies completed or underway to study the dietary effects of plant flavonoids on cardiovascular diseases.^[55]

However, population-based studies have failed to show a strong beneficial effect^[56] which might be due to the considerably lower intake in the habitual diet of those investigated.

Antibacterial[edit]

Flavonoids have been shown to have (a) direct antibacterial activity, (b) synergistic activity with antibiotics, and (c) the ability to suppress bacterialvirulence factors in numerous in vitro and a limited number of in vivo studies.^[27][57] Noteworthy among the in vivo studies^[58][59][60] is the finding that oral quercetin protects guinea pigs against the Group 1 carcinogen Helicobacter pylori.^[60] Researchers from the European Prospective Investigation into Cancer and Nutrition have speculated this may be one reason why dietary flavonoid intake is associated with reduced gastric carcinoma risk in European women.^[61] Additional in vivo and clinical research is needed to determine if flavonoids could be used as pharmaceutical drugs for the treatment of bacterial infection, or whether dietary flavonoid intake offers any protection against infection.

Synthesis, detection, quantification, and semi-synthetic alterations[edit]

Color spectrum[edit]

Flavonoid synthesis in plants is induced by light color spectrums at both high and low energy radiations. Low energy radiations are accepted byphytochrome, while high energy radiations are accepted by carotenoids, flavins, cryptochromes in addition to phytochromes. Thephotomorphogenic process of phytochome-mediated flavonoid biosynthesis has been observed in Amaranthus, barley, maize, Sorghum and turnip. Red light promotes flavonoid synthesis.^[62]

Availability through microorganisms[edit]

Several recent research articles have demonstrated the efficient production of flavonoid molecules from genetically engineered microorganisms.^[63][64][65]

Tests for detection[edit]

Shinoda test

Four pieces of magnesium filings are added to the ethanolic extract followed by few drops of concentrated hydrochloric acid. A pink or red colour indicates the presence of flavonoid.^[66] Colours varying from orange to red indicated flavones, red to crimson indicated flavonoids, crimson to magenta indicated flavonones.

Sodium hydroxide test

About 5 mg of the compound is dissolved in water, warmed and filtered. 10% aqueous sodium hydroxide is added to 2 ml of this solution. This produces a yellow coloration. A change in color from yellow to colorless on addition of dilute hydrochloric acid is an indication for the presence of flavonoids.^[67]

p-Dimethylaminocinnamaldehyde test

A colorimetric assay based upon the reaction of A-rings with the chromogen p-dimethylaminocinnamaldehyde (DMACA) has been developed for flavanoids in beer that can be compared with the vanillin procedure.^[68]

Quantification[edit]

Lamaison and Carnet have designed a test for the determination of the total flavonoid content of a sample (AlCI₃ method). After proper mixing of the sample and the reagent, the mixture is incubated for 10 minutes at ambient temperature and the absorbance of the solution is read at 440 nm. Flavonoid content is expressed in mg/g of quercetin.^[69]

Semi-synthetic alterations[edit]

Immobilized Candida antarctica lipase can be used to catalyze the regioselective acylation of flavonoids.^[70]

See also[edit]

• Phytochemical
• List of antioxidants in food
• List of phytochemicals in food
• Phytochemistry
• Secondary metabolites
• Homoisoflavonoids, related chemicals with a 16 carbons skeleton

References[edit]

1. Jump up^ McNaught, Alan D; Wilkinson, Andrew; IUPAC (1997), "IUPAC Compendium of Chemical Terminology", IUPAC Compendium of Chemical Terminology (2 ed.), Oxford: Blackwell Scientific, ISBN 0-9678550-9-8, doi:10.1351/goldbook.F02424
2. Jump up^ "The Gold Book". 2009. ISBN 0-9678550-9-8.doi:10.1351/goldbook. Retrieved 16 September 2012. |chapter=ignored (help)
3. Jump up^ Galeotti, F; Barile, E; Curir, P; Dolci, M; Lanzotti, V (2008). "Flavonoids from carnation (Dianthus caryophyllus) and their antifungal activity". Phytochemistry Letters. 1: 44–48.doi:10.1016/j.phytol.2007.10.001.
4. Jump up^ Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N (October 2007). "Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health". Biotechnology Journal. 2(10): 1214–34. PMID 17935117. doi:10.1002/biot.200700084.
5. Jump up^ Isolation of a UDP-glucose: Flavonoid 5-O-glucosyltransferase gene and expression analysis of anthocyanin biosynthetic genes in herbaceous peony (Paeonia lactiflora Pall.). Da Qiu Zhao, Chen Xia Han, Jin Tao Ge and Jun Tao, Electronic Journal of Biotechnology, 15 November 2012, Volume 15, Number 6, doi:10.2225/vol15-issue6-fulltext-7
6. Jump up^ Spencer JP (2008). "Flavonoids: modulators of brain function?". British Journal of Nutrition. 99: ES60–77. PMID 18503736.doi:10.1017/S0007114508965776.
7. ^ Jump up to:^{a b c d e f g h i j} USDA's Database on the Flavonoid Content
8. Jump up^ Ayoub M, de Camargo AC, Shahidi F (2016). "Antioxidants and bioactivities of free, esterified and insoluble-bound phenolics from berry seed meals". Food Chemistry. 197 (Part A): 221–232.doi:10.1016/j.foodchem.2015.10.107.
9. Jump up^ "The devil in the dark chocolate". Lancet. 370 (9605): 2070. 2007.PMID 18156011. doi:10.1016/S0140-6736(07)61873-X.
10. Jump up^ Serafini M, Bugianesi R, Maiani G, Valtuena S, De Santis S, Crozier A (2003). "Plasma antioxidants from chocolate". Nature. 424 (6952): 1013. Bibcode:2003Natur.424.1013S. PMID 12944955.doi:10.1038/4241013a.
11. Jump up^ Serafini M, Bugianesi R, Maiani G, Valtuena S, De Santis S, Crozier A (2003). "Nutrition: milk and absorption of dietary flavanols". Nature.424 (6952): 1013. Bibcode:2003Natur.424.1013S. PMID 12944955.doi:10.1038/4241013a.
12. Jump up^ Roura E, et al. (2007). "Milk Does Not Affect the Bioavailability of Cocoa Powder Flavonoid in Healthy Human" (PDF). Ann Nutr Metab.51: 493–498. doi:10.1159/000111473.
13. Jump up^ de Camargo AC, Regitano-d'Arce MA, Gallo CR, Shahidi F (2015)."Gamma-irradiation induced changes in microbiological status, phenolic profile and antioxidant activity of peanut skin". Journal of Functional Foods. 12: 129–143. doi:10.1016/j.jff.2014.10.034.
14. Jump up^ Chukwumah Y, Walker LT, Verghese M (2009). "Peanut skin color: a biomarker for total polyphenolic content and antioxidative capacities of peanut cultivars". Int J Mol Sci. 10 (11): 4941–52. PMC 2808014 .PMID 20087468. doi:10.3390/ijms10114941.
15. Jump up^ "Flavonoids - Linus Pauling Institute - Oregon State University". Retrieved 26 February 2016.
16. ^ Jump up to:^a b c d Vogiatzoglou, A; Mulligan, A. A.; Lentjes, M. A.; Luben, R. N.; Spencer, J. P.; Schroeter, H; Khaw, K. T.; Kuhnle, G. G. (2015)."Flavonoid intake in European adults (18 to 64 years)". PLoS ONE. 10(5): e0128132. PMC 4444122 . PMID 26010916.doi:10.1371/journal.pone.0128132.
17. ^ Jump up to:^a b Chun, O. K.; Chung, S. J.; Song, W. O. (2007). "Estimated dietary flavonoid intake and major food sources of U.S. Adults". The Journal of Nutrition. 137 (5): 1244–52. PMID 17449588.
18. Jump up^ "FDA approved drug products". US Food and Drug Administration. Retrieved 8 November 2013.
19. Jump up^ "Health Claims Meeting Significant Scientific Agreement". US Food and Drug Administration. Retrieved 8 November 2013.
20. ^ Jump up to:^a b EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)2, 3 European Food Safety Authority (EFSA), Parma, Italy (2010)."Scientific Opinion on the substantiation of health claims related to various food(s)/food constituent(s) and protection of cells from premature aging, antioxidant activity, antioxidant content and antioxidant properties, and protection of DNA, proteins and lipids from oxidative damage pursuant to Article 13(1) of Regulation (EC) No 1924/20061"(PDF). EFSA Journal. 8 (2): 1489. doi:10.2903/j.efsa.2010.1489.
21. Jump up^ "Inspections, Compliance, Enforcement, and Criminal Investigations (Flavonoid Sciences)". US Food and Drug Administration. Retrieved8 November 2013.
22. Jump up^ "Inspections, Compliance, Enforcement, and Criminal Investigations (Unilever, Inc.)". US Food and Drug Administration. Retrieved25 October 2013.
23. Jump up^ "Lipton green tea is a drug". NutraIngredients-USA.com. Retrieved25 October 2013.
24. Jump up^ "Fruits Are Good for Your Health? Not So Fast: FDA Stops Companies From Making Health Claims About Foods". TheDailyGreen.com. Retrieved 25 October 2013.
25. ^ Jump up to:^a b Yamamoto Y, Gaynor RB (2001). "Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer". Journal of Clinical Investigation. 107 (2): 135–42.PMC 199180 . PMID 11160126. doi:10.1172/JCI11914.
26. ^ Jump up to:^a b c Cazarolli LH, Zanatta L, Alberton EH, Figueiredo MS, Folador P, Damazio RG, Pizzolatti MG, Silva FR (2008). "Flavonoids: Prospective Drug Candidates". Mini-Reviews in Medicinal Chemistry. 8 (13): 1429–1440. PMID 18991758. doi:10.2174/138955708786369564.
27. ^ Jump up to:^a b Cushnie TP, Lamb AJ (2011). "Recent advances in understanding the antibacterial properties of flavonoids". International Journal of Antimicrobial Agents. 38 (2): 99–107. PMID 21514796.doi:10.1016/j.ijantimicag.2011.02.014.
28. Jump up^ Manner S, Skogman M, Goeres D, Vuorela P, Fallarero A (2013)."Systematic exploration of natural and synthetic flavonoids for the inhibition of Staphylococcus aureus biofilms". International Journal of Molecular Sciences. 14 (10): 19434–19451. PMC 3821565 .PMID 24071942. doi:10.3390/ijms141019434.
29. ^ Jump up to:^a b Cushnie TP, Lamb AJ (2005). "Antimicrobial activity of flavonoids" (PDF). International Journal of Antimicrobial Agents. 26(5): 343–356. PMID 16323269.doi:10.1016/j.ijantimicag.2005.09.002.
30. ^ Jump up to:^a b Friedman M (2007). "Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas". Molecular Nutrition and Food Research. 51 (1): 116–134. PMID 17195249.doi:10.1002/mnfr.200600173.
31. Jump up^ de Sousa RR, Queiroz KC, Souza AC, Gurgueira SA, Augusto AC, Miranda MA, Peppelenbosch MP, Ferreira CV, Aoyama H (2007). "Phosphoprotein levels, MAPK activities and NFkappaB expression are affected by fisetin". J Enzyme Inhib Med Chem. 22 (4): 439–444.PMID 17847710. doi:10.1080/14756360601162063.
32. Jump up^ Schuier M, Sies H, Illek B, Fischer H (2005). "Cocoa-related flavonoids inhibit CFTR-mediated chloride transport across T84 human colon epithelia". J. Nutr. 135 (10): 2320–5. PMID 16177189.
33. Jump up^ Esselen M, Fritz J, Hutter M, Marko D (2009). "Delphinidin Modulates the DNA-Damaging Properties of Topoisomerase II Poisons". Chemical Research in Toxicology. 22 (3): 554–64. PMID 19182879.doi:10.1021/tx800293v.
34. Jump up^ Bandele OJ, Clawson SJ, Osheroff N (2008). "Dietary polyphenols as topoisomerase II poisons: B-ring substituents determine the mechanism of enzyme-mediated DNA cleavage enhancement". Chemical Research in Toxicology. 21 (6): 1253–1260. PMC 2737509 .PMID 18461976. doi:10.1021/tx8000785.
35. Jump up^ Barjesteh van Waalwijk van Doorn-Khosrovani S, Janssen J, Maas LM, Godschalk RW, Nijhuis JG, van Schooten FJ (2007). "Dietary flavonoids induce MLL translocations in primary human CD34+ cells".Carcinogenesis. 28 (8): 1703–9. PMID 17468513.doi:10.1093/carcin/bgm102.
36. Jump up^ Lotito SB, Frei B (2006). "Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon?". Free Radic. Biol. Med. 41 (12): 1727–46. PMID 17157175.doi:10.1016/j.freeradbiomed.2006.04.033.
37. Jump up^ Williams RJ, Spencer JP, Rice-Evans C (2004). "Flavonoids: antioxidants or signalling molecules?". Free Radical Biology & Medicine.36 (7): 838–49. PMID 15019969.doi:10.1016/j.freeradbiomed.2004.01.001.
38. Jump up^ Stauth D (5 March 2007). "Studies force new view on biology of flavonoids". EurekAlert!, Adapted from a news release issued by Oregon State University.
39. Jump up^ Ravishankar D, Rajora AK, Greco F, Osborn HM (2013). "Flavonoids as prospective compounds for anti-cancer therapy". The International Journal of Biochemistry & Cell Biology. 45 (12): 2821–2831.PMID 24128857. doi:10.1016/j.biocel.2013.10.004.
40. Jump up^ Manach C, Mazur A, Scalbert A (2005). "Polyphenols and prevention of cardiovascular diseases". Current opinion in lipidology. 16 (1): 77–84.PMID 15650567. doi:10.1097/00041433-200502000-00013.
41. Jump up^ Babu PV, Liu D, Gilbert ER (2013). "Recent advances in understanding the anti-diabetic actions of dietary flavonoids". The Journal of Nutritional Biochemistry. 24 (11): 1777–1789. PMC 3821977 . PMID 24029069. doi:10.1016/j.jnutbio.2013.06.003.
42. Jump up^ Ferretti G, Bacchetti T, Masciangelo S, Saturni L (2012). "Celiac Disease, Inflammation and Oxidative Damage: A Nutrigenetic Approach". Nutrients. 4 (12): 243–257. PMC 3347005 .PMID 22606367. doi:10.3390/nu4040243.
43. ^ Jump up to:^a b c Izzi V, Masuelli L, Tresoldi I, Sacchetti P, Modesti A, Galvano F, Bei R (2012). "The effects of dietary flavonoids on the regulation of redox inflammatory networks". Frontiers in bioscience (Landmark edition). 17(7): 2396–2418. PMID 22652788. doi:10.2741/4061.
44. Jump up^ Gomes A, Couto D, Alves A, Dias I, Freitas M, Porto G, Duarte JA, Fernandes E (2012). "Trihydroxyflavones with antioxidant and anti-inflammatory efficacy". BioFactors. 38 (5): 378–386. PMID 22806885.doi:10.1002/biof.1033.
45. Jump up^ Chang CF, Cho S, Wang J (Apr 2014). "(-)-Epicatechin protects hemorrhagic brain via synergistic Nrf2 pathways". Ann Clin Transl Neurol. 1 (4): 258–271. PMC 3984761 . PMID 24741667.doi:10.1002/acn3.54.
46. Jump up^ Martinez-Micaelo N, González-Abuín N, Ardèvol A, Pinent M, Blay MT (2012). "Procyanidins and inflammation: Molecular targets and health implications". BioFactors. 38 (4): 257–265. PMID 22505223.doi:10.1002/biof.1019.
47. Jump up^ Romagnolo DF, Selmin OI (2012). "Flavonoids and cancer prevention: a review of the evidence". J Nutr Gerontol Geriatr. 31 (3): 206–38.PMID 22888839. doi:10.1080/21551197.2012.702534.
48. Jump up^ González CA, Sala N, Rokkas T (2013). "Gastric cancer: epidemiologic aspects". Helicobacter. 18 (Supplement 1): 34–38.PMID 24011243. doi:10.1111/hel.12082.
49. Jump up^ Woo HD, Kim J (2013). "Dietary flavonoid intake and smoking-related cancer risk: a meta-analysis". PLoS ONE. 8 (9): e75604.Bibcode:2013PLoSO...875604W. PMC 3777962 .PMID 24069431. doi:10.1371/journal.pone.0075604.
50. Jump up^ Higdon, J; Drake, V; Frei, B (March 2009). "Non-Antioxidant Roles for Dietary Flavonoids: Reviewing the relevance to cancer and cardiovascular diseases". Nutraceuticals World. Rodman Media. Retrieved 24 November 2013.
51. Jump up^ van Dam RM, Naidoo N, Landberg R (2013). "Dietary flavonoids and the development of type 2 diabetes and cardiovascular diseases".Current Opinion in Lipidology. 24 (1): 25–33. PMID 23254472.doi:10.1097/MOL.0b013e32835bcdff.
52. Jump up^ Tangney CC, Rasmussen HE (2013). "Polyphenols, Inflammation, and Cardiovascular Disease". Current Atherosclerosis Reports. 15 (5): 324. PMC 3651847 . PMID 23512608. doi:10.1007/s11883-013-0324-x.
53. Jump up^ Siasos G, Tousoulis D, Tsigkou V, Kokkou E, Oikonomou E, Vavuranakis M, Basdra EK, Papavassiliou AG, Stefanadis C (2013). "Flavonoids in atherosclerosis: An overview of their mechanisms of action". Current medicinal chemistry. 20 (21): 2641–2660.PMID 23627935. doi:10.2174/0929867311320210003.
54. Jump up^ Cappello, AR, Dolce V, Iacopetta D, Martello M, Fiorillo M, Curcio R, Muto L, Dhanyalayam D. (2015). "Bergamot (Citrus bergamia Risso) Flavonoids and Their Potential Benefits in Human Hyperlipidemia and Atherosclerosis: an Overview". Mini-Reviews in Medicinal Chemistry. 16(8): 1–11. PMID 26156545.doi:10.2174/1389557515666150709110222.
55. Jump up^ Search Results. "Flavonoids in cardiovascular disease clinical trials". Clinicaltrials.gov. US National Institutes of Health. RetrievedNovember 24, 2013.
56. Jump up^ Wang X; Ouyang YY; Liu J; Zhao G (January 2014). "Flavonoid intake and risk of CVD: a systematic review and meta-analysis of prospective cohort studies". The British journal of nutrition. 111 (1): 1–11.PMID 23953879. doi:10.1017/S000711451300278X.
57. Jump up^ Taylor PW, Hamilton-Miller JM, Stapleton PD (2005). "Antimicrobial properties of green tea catechins". Food Science and Technology Bulletin. 2 (7): 71–81. PMC 2763290 . PMID 19844590.doi:10.1616/1476-2137.14184.
58. Jump up^ Choi O, Yahiro K, Morinaga N, Miyazaki M, Noda M (2007). "Inhibitory effects of various plant polyphenols on the toxicity of Staphylococcal alpha-toxin". Microbial Pathogenesis. 42 (5–6): 215–224.PMID 17391908. doi:10.1016/j.micpath.2007.01.007.
59. Jump up^ Oh DR, Kim JR, Kim YR (2010). "Genistein inhibits Vibrio vulnificus adhesion and cytotoxicity to HeLa cells". Archives of Pharmacal Research. 33 (5): 787–792. PMID 20512479. doi:10.1007/s12272-010-0520-y.
60. ^ Jump up to:^a b González-Segovia R, Quintanar JL, Salinas E, Ceballos-Salazar R, Aviles-Jiménez F, Torres-López J (2008). "Effect of the flavonoid quercetin on inflammation and lipid peroxidation induced by Helicobacter pylori in gastric mucosa of guinea pig". Journal of Gastroenterology. 43(6): 441–447. PMID 18600388. doi:10.1007/s00535-008-2184-7.
61. Jump up^ Zamora-Ros R, Agudo A, Luján-Barroso L, Romieu I, Ferrari P, Knaze V, Bueno-de-Mesquita HB, Leenders M, Travis RC, Navarro C, Sánchez-Cantalejo E, Slimani N, Scalbert A, Fedirko V, Hjartåker A, Engeset D, Skeie G, Boeing H, Förster J, Li K, Teucher B, Agnoli C, Tumino R, Mattiello A, Saieva C, Johansson I, Stenling R, Redondo ML, Wallström P, Ericson U, Khaw KT, Mulligan AA, Trichopoulou A, Dilis V, Katsoulis M, Peeters PH, Igali L, Tjønneland A, Halkjær J, Touillaud M, Perquier F, Fagherazzi G, Amiano P, Ardanaz E, Bredsdorff L, Overvad K, Ricceri F, Riboli E, González CA (2012). "Dietary flavonoid and lignan intake and gastric adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study". American Journal of Clinical Nutrition. 96 (6): 1398–1408. PMID 23076618.doi:10.3945/ajcn.112.037358.
62. Jump up^ Sinha, Rajiv Kumar (2004-01-01). Modern Plant Physiology. CRC Press. p. 457. ISBN 9780849317149.
63. Jump up^ Hwang EI, Kaneko M, Ohnishi Y, Horinouchi S (May 2003)."Production of plant-specific flavanones by Escherichia coli containing an artificial gene cluster". Appl. Environ. Microbiol. 69 (5): 2699–706.PMC 154558 . PMID 12732539. doi:10.1128/AEM.69.5.2699-2706.2003.
64. Jump up^ Trantas E, Panopoulos N, Ververidis F (2009). "Metabolic engineering of the complete pathway leading to heterologous biosynthesis of various flavonoids and stilbenoids in Saccharomyces cerevisiae". Metabolic Engineering. 11 (6): 355–366. PMID 19631278.doi:10.1016/j.ymben.2009.07.004.
65. Jump up^ Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N (2007). "Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part II: Reconstruction of multienzyme pathways in plants and microbes". Biotechnology Journal.2 (10): 1235–49. PMID 17935118. doi:10.1002/biot.200700184.
66. Jump up^ Yisa, Jonathan (2009). "Phytochemical Analysis and Antimicrobial Activity Of Scoparia Dulcis and Nymphaea Lotus". Australian Journal of Basic and Applied Sciences. 3 (4): 3975–3979.
67. Jump up^ Bello IA, Ndukwe GI, Audu OT, Habila JD (2011). "A bioactive flavonoid from Pavetta crassipes K. Schum". Organic and Medicinal Chemistry Letters. 1 (1): 14. PMC 3305906 . PMID 22373191.doi:10.1186/2191-2858-1-14.
68. Jump up^ A new colourimetric assay for flavonoids in pilsner beers. Jan A. Delcour and Didier Janssens de Varebeke, Journal of the Institute of Brewing, January–February 1985, Volume 91, Issue 1, pages 37–40,doi:10.1002/j.2050-0416.1985.tb04303.x
69. Jump up^ Lamaison, JL; Carnet, A (1991). "Teneurs en principaux flavonoides des fleurs de Cratageus monogyna Jacq et de Cratageus Laevigata (Poiret D.C) en Fonction de la vegetation". Plantes Medicinales Phytotherapie. 25: 12–16.
70. Jump up^ Passicos E, Santarelli X, Coulon D (2004). "Regioselective acylation of flavonoids catalyzed by immobilized Candida antarctica lipase under reduced pressure". Biotechnol Lett. 26 (13): 1073–1076.PMID 15218382. doi:10.1023/B:BILE.0000032967.23282.15.

Further reading[edit]

• Andersen, Ø.M. / Markham, K.R. (2006). Flavonoids: Chemistry, Biochemistry and Applications. CRC Press. ISBN 978-0-8493-2021-7
• Grotewold, Erich (2007). The Science of Flavonoids. Springer. ISBN 978-0-387-74550-3
• Comparative Biochemistry of the Flavonoids, by J.B. Harborne, 1967 (Google Books)
• The systematic identification of flavonoids, by T.J. Mabry, K.R. Markham and M.B. Thomas, 1970, doi:10.1016/0022-2860(71)87109-0

External links[edit]

• Micronutrient Information Center – Flavonoids, Linus Pauling Institute, Oregon State University, Corvallis, 2015

Databases[edit]

• USDA Database for the Flavonoid Content of Selected Foods, Release 3.1 (December 2013); data for 506 foods in the 5 subclasses of flavonoids provided in a separate PDF updated May 2014

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com