Phytoestrogens as bioactive ingredients in functional foods: Canadian regulatory update

Some food products naturally contain phytoestrogens, but there are few in Western diets that are significant sources. The foods that are the most significant sources are soy beans, containing isoflavones, and flaxseed, which contains lignans. These foods have, however, until recently been relatively little used in Canada and the United States in the human diet. While the Japanese diet contains from 20 to 80 mg of isoflavones per day, Canadian and U.S. diets tend to be below 1 mg/day in the absence of soy protein. The number of foods sold in the West that have ingredients derived from soybeans has been increasing. Many of these have soybean oil, soy protein, or other ingredients serving functional roles in the food. However, with increasing interest among consumers in dietary choices that help to improve health and reduce risk of disease, products in which soy is featured are quite readily available, and it is common, at least in Canada, to find bread and other bakery products with flaxseed added. Soy foods sales in the United States increased at a 15% compounded annually growth rate between 1992 and 2003, with a major increase occurring between 2000 and 2001 (1). Growth rates are reported to have declined somewhat in 2004 (2). The U.S. Food and Drug Administration approval of a health claim associating soy protein intake with reduced risk of heart disease in 1999 is attributed with fueling the very sizable growth since 2000. The claim identifies 25 g/day as the amount needed to derive the claimed health benefit. Because the isoflavone content of soy products is highly variable, depending on the method of processing (3), it is difficult to estimate quantitatively the impact of the increased rate of soy product consumption on soy isoflavone intake, although an overall increase can be expected. In contrast,     

Synthesis of Pyrido[2′,3′: 3,4]pyrazolo[1,5‐a]pyrimidine,Pyrido[2′,3′:3,4]pyrazolo[5,1‐c][1,2,4]triazine,and Pyrazolyl Oxadiazolylthieno[2,3‐b]pyridine Derivatives

6‐(2‐Thienyl)‐4‐(trifluoromethyl)‐1H‐pyrazolo[3,4‐b]pyridine‐3‐amine reacted with different active methylene compounds to afford pyridopyrazolopyrimidine derivatives. On the other hand, it reacted with some halo compounds to give the imidazo[1′,2′:1,5]pyrazolo[3,4‐b]pyridine derivatives. Also, it diazotized to give the corresponding diazonium chloride that is coupled with several active methylene compounds to give the corresponding triazine derivatives. Furthermore, compound 3‐amino‐6‐(2(thienyl)‐4‐(trifluoromethyl)thieno[2,3‐b]pyridine‐2‐carbohydrazide reacted with some β‐dicarbonyl compounds and some sulfur‐containing compounds to afford the corresponding pyrazolyl oxadiazolylthieno[2,3‐b]pyridine derivatives.     

Comparison of ALA- and ALA hexyl-ester-induced PpIX depth distribution in human skin carcinoma

Photodynamic therapy (PDT) based on the use of photoactivable porphyrins, such as protoporphyrin IX (PpIX), induced by the topical application of amino-levulinic acid (ALA) or its derivatives, ALA methyl-ester (m-ALA), is a treatment for superficial basal cell carcinoma (BCC), with complete response rates of over 80%. However, in the case of deep, nodular-ulcerative lesions, the complete response rates are lower, possibly related to a lower bioavailability of PpIX. Previous in vitro skin permeation studies demonstrated an increased penetration of amino-levulinic acid hexyl-ester (h-ALA) over ALA. In this study, we tested the validity of this approach in vivo on human BCCs. An emulsion containing 20% ALA (w/w) and preparations of h-ALA at different concentrations were applied topically to the normal skin of Caucasian volunteers to compare the PpIX fluorescence intensities with an optical fiber-based spectrofluorometer. In addition, the PpIX depth distribution and fluorescence intensity in 26 BCCs were investigated by fluorescence microscopy following topical application of 20% ALA and 1% h-ALA. We found that, for application times up to 24h, h-ALA is identical to ALA as a PpIX precursor with respect to PpIX fluorescence intensity, depth of penetration, and distribution in basal cell carcinoma, but has the added advantage that much smaller h-ALA concentrations can be used (up to a factor 13). We observed a non-homogenous distribution in BCCs with both precursors, independent of the histological type and depth of invasion in the dermis.     

Targeted phase II metabolites profiling as new screening strategy to investigate natural steroid abuse in animal breeding

The use of steroid hormones as growth promoters in cattle is banned within the European Union since 1988 but can still be fraudulently employed in animal breeding farms for anabolic purposes. While efficient targeted confirmatory methods have been implemented in control laboratories for many years, fast and reliable screening methods are still required, especially in the case of natural hormones abuse, but more globally for new "fishing" strategies allowing to reveal the use of even unknown anabolic agents. The development of focused profiling or untargeted metabolomic approaches is thus emerging in this context. The present study was a focused profiling study using steroids phase II metabolites, with the aim to get a better understanding of the steroid metabolism disruptions after exogenous administration of androstenedione and finally reveal potential biomarkers signing its administration. A sample preparation procedure was first developed, based on a separation of 31 glucuronide and sulphate conjugate compounds using an anion exchange SPE system. Each fraction was then analysed by UPLC-MS/MS in MRM mode showing a rapid (between 4h and 4 days after treatment) and huge excretion of several direct metabolites of androstenedione such as etiocholanolone-glucuronide or epiandrosterone-sulphate.     

Synthesis of Unsymmetrical Ureas and S‐Thiocarbamates under Catalyst‐free Conditions in a [BMIM]BF4 Ionic Liquid

Unsymmetrical ureas and S‐thiocarbamates were prepared in good to excellent yields by direct condensation of phenylurea with amines and thiols in 1‐butyl‐3‐methylimidazolium tetrafluoroborate ([BMIM]BF₄) without the addition of any additives. The [BMIM]BF₄ ionic liquid is a mild medium and can be recycled and reused several times.     

The onset of calcium carbonate nucleation: a density functional theory molecular dynamics and hybrid microsolvation/continuum study

Density functional theory (Perdew-Burke-Ernzerhof) based methods have been used to study the structure and hydration environment of the building blocks of CaCO 3 in aqueous solutions of calcium bicarbonate and calcium carbonate. Car-Parrinello molecular dynamics simulations of Ca(2+)/CO3(2-) and Ca (2+)/HCO3(-) in explicit water were performed to investigate the formation of CaCO3 and the hydration shell of the solvated hetero-ion pair. Our simulations show that the formation of the monomer of CaCO3 occurs with an associative mechanism and that the dominant building block of calcium (bi)carbonate in aqueous solution is Ca[eta(1)-(H)CO3](H2O)5, i.e., the preferred hydration number is five, while the (bi)carbonate is coordinated to the calcium in a monodentate mode. This result agrees with static calculations, where a hybrid approach using a combination of explicit solvent molecules and a polarizable continuum model has been applied to compute the solvation free energies of calcium bicarbonate species. Furthermore, the discrete-continuum calculations predict that the Ca(HCO3)2 and Ca(HCO3)3(-) species are stable in an aqueous environment preferentially as Ca(HCO3)2(H2O)4 and Ca(HCO3)3(H2O)2(-), respectively.     

Water-Driven Synthesis of Deep-Blue Perovskite Colloidal Quantum Wells for Electroluminescent Devices

Perovskite colloidal quantum wells (QWs) are promising to realize narrow deep-blue emission, but the poor optical performance and stability suppress their practical application. Here, we creatively propose a water-driven synthesis strategy to obtain size-homogenized and strongly confined deep-blue CsPbBr₃ QWs, corresponding to three monolayers, which emit at the deep-blue wavelength of 456 nm. The water controls the orientation and distribution of the ligands on the surface of the nanocrystals, thus inducing orientated growth through the Ostwald ripening process by phagocytizing unstable nanocrystals to form well-crystallized QWs. These QWs present remarkable stability and high photoluminescence quantum yield of 94 %. Furthermore, we have prepared light-emitting diodes based on the QWs via the all-solution fabrication strategy, achieving an external quantum efficiency of 1 % and luminance of 2946 cd m⁻², demonstrating state-of-the-art brightness for perovskite QW-based LEDs.     

Dipyrrinato-Iridium(III) Complexes for Application in Photodynamic Therapy and Antimicrobial Photodynamic Inactivation

The generation of bio-targetable photosensitizers is of utmost importance to the emerging field of photodynamic therapy and antimicrobial (photo-)therapy. A synthetic strategy is presented in which chelating dipyrrin moieties are used to enhance the known photoactivity of iridium(III) metal complexes. Formed complexes can thus be functionalized in a facile manner with a range of targeting groups at their chemically active reaction sites. Dipyrrins with N- and O-substituents afforded (dipy)iridium(III) complexes via complexation with the respective Cp*-iridium(III) and ppy-iridium(III) precursors (dipy=dipyrrinato, Cp*=pentamethyl-η⁵-cyclopentadienyl, ppy=2-phenylpyridyl). Similarly, electron-deficient [Ir^III(dipy)(ppy)₂] complexes could be used for post-functionalization, forming alkenyl, alkynyl and glyco-appended iridium(III) complexes. The phototoxic activity of these complexes has been assessed in cellular and bacterial assays with and without light; the [Ir^III(Cl)(Cp*)(dipy)] complexes and the glyco-substituted iridium(III) complexes showing particular promise as photomedicine candidates. Representative crystal structures of the complexes are also presented.     

Valorization of Different Fractions from Butiá Pomace by Pyrolysis: H2 Generation and Use of the Biochars for CO2 Capture

This work valorizes butiá pomace (Butia capitata) using pyrolysis to prepare CO₂ adsorbents. Different fractions of the pomace, like fibers, endocarps, almonds, and deoiled almonds, were characterized and later pyrolyzed at 700 °C. Gas, bio-oil, and biochar fractions were collected and characterized. The results revealed that biochar, bio-oil, and gas yields depended on the type of pomace fraction (fibers, endocarps, almonds, and deoiled almonds). The higher biochar yield was obtained by endocarps (31.9%wt.). Furthermore, the gas fraction generated at 700 °C presented an H₂ content higher than 80%vol regardless of the butiá fraction used as raw material. The biochars presented specific surface areas reaching 220.4 m² g⁻¹. Additionally, the endocarp-derived biochar presented a CO₂ adsorption capacity of 66.43 mg g⁻¹ at 25 °C and 1 bar, showing that this material could be an effective adsorbent to capture this greenhouse gas. Moreover, this capacity was maintained for 5 cycles. Biochars produced from butiá precursors without activation resulted in a higher surface area and better performance than some activated carbons reported in the literature. The results highlighted that pyrolysis could provide a green solution for butiá agro-industrial wastes, generating H₂ and an adsorbent for CO₂.