The Effects of Nanomaterials as Endocrine Disruptors

In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited.     

Protein immobilization on polyvinylphenol via tyrosine oxidation of proteins catalyzed by horseradish peroxidase

Surface functionalization of polymeric materials holds great potential in biological and medical fields with the aim toward realizing desired biological reactions (e.g., cell adhesion, and immune response), especially for proteins which have physiological functions. The objective was to examine characteristics of a unique and facile protein immobilization on a phenol-containing polymeric material utilizing horseradish peroxidase (HRP) and tyrosine residues of target proteins as catalyst and substrates, respectively. Cy3-labeled streptavidin exhibited the predicted immobilization behavior since the reaction effectively proceeded in the presence of HRP-H₂O₂ and on the surface of polyvinylphenol. This procedure was applicable to other representative proteins, that is, bovine serum albumin, immunoglobulin G (IgG), and HRP as substrates. However, IgG exhibited anomalous reaction behavior under the present reaction condition probably due to its rich tyrosine content. Undesired immobilization of HRP was minimized by addition of large amounts of a competitive substrate. The biotin-binding affinity of streptavidin-immobilized surface was confirmed to maintain activity even after the immobilization procedure.     

Antifungal Peptides and Proteins to Control Toxigenic Fungi and Mycotoxin Biosynthesis

The global challenge to prevent fungal spoilage and mycotoxin contamination on food and feed requires the development of new antifungal strategies. Antimicrobial peptides and proteins (AMPs) with antifungal activity are gaining much interest as natural antifungal compounds due to their properties such as structure diversity and function, antifungal spectrum, mechanism of action, high stability and the availability of biotechnological production methods. Given their multistep mode of action, the development of fungal resistance to AMPs is presumed to be slow or delayed compared to conventional fungicides. Interestingly, AMPs also accomplish important biological functions other than antifungal activity, including anti-mycotoxin biosynthesis activity, which opens novel aspects for their future use in agriculture and food industry to fight mycotoxin contamination. AMPs can reach intracellular targets and exert their activity by mechanisms other than membrane permeabilization. The mechanisms through which AMPs affect mycotoxin production are varied and complex, ranging from oxidative stress to specific inhibition of enzymatic components of mycotoxin biosynthetic pathways. This review presents natural and synthetic antifungal AMPs from different origins which are effective against mycotoxin-producing fungi, and aims at summarizing current knowledge concerning their additional effects on mycotoxin biosynthesis. Antifungal AMPs properties and mechanisms of action are also discussed.     

Spectroscopic investigations, characterization and chemical sensor application of composite Langmuir-Schäfer films of anthocyanins and oligophenylenevinylene derivatives

Anthocyanins, extracted from grape skin (Vitis vinifera), were dissolved in ultrapure aqueous subphase and an oligophenylenevinylene derivative was spread on the subphase surface. Such oligomer was chosen as anionic counterpart of hydrosoluble anthocyanins in order to perform a Langmuir-Schäfer film of the dyad. Interface interactions between oligophenylenevinylene derivative and anthocyanins were studied by Brewster angle microscopy and reflection spectroscopy. Additionally, the oligomer exhibits a chemical structure able to ensure an enhancement of the stability under UV-visible irradiations of the film of the dyad without any variation of the natural pigment absorption in the visible range. The visible spectra of cast anthocyanins film and Langmuir-Schäfer oligomer/anthocyanins film after exposure to 254 nm irradiation showed a remarkable increase of the film stability, probably due to the screening effect of the oligomer. Preliminary test of a Langmuir-Schäfer film of oligophenylenevinylene derivative/anthocyanins as a herbicide sensor showed that sensing is completely reversible, stable and repeatable.     

Sandbur Drought Tolerance Reflects Phenotypic Plasticity Based on the Accumulation of Sugars,Lipids, and Flavonoid Intermediates and the Scavenging of Reactive Oxygen Species in the Root

The perennial grass Cenchrus spinifex (common sandbur) is an invasive species that grows in arid and semi-arid regions due to its remarkable phenotypic plasticity, which confers the ability to withstand drought and other forms of abiotic stress. Exploring the molecular mechanisms of drought tolerance in common sandbur could lead to the development of new strategies for the protection of natural and agricultural environments from this weed. To determine the molecular basis of drought tolerance in C. spinifex, we used isobaric tags for relative and absolute quantitation (iTRAQ) to identify proteins differing in abundance between roots growing in normal soil and roots subjected to moderate or severe drought stress. The analysis of these proteins revealed that drought tolerance in C. spinifex primarily reflects the modulation of core physiological activities such as protein synthesis, transport and energy utilization as well as the accumulation of flavonoid intermediates and the scavenging of reactive oxygen species. Accordingly, plants subjected to drought stress accumulated sucrose, fatty acids, and ascorbate, shifted their redox potential (as determined by the NADH/NAD ratio), accumulated flavonoid intermediates at the expense of anthocyanins and lignin, and produced less actin, indicating fundamental reorganization of the cytoskeleton. Our results show that C. spinifex responds to drought stress by coordinating multiple metabolic pathways along with other adaptations. It is likely that the underlying metabolic plasticity of this species plays a key role in its invasive success, particularly in semi-arid and arid environments.     

Natural Autoimmunity to Selenoprotein P Impairs Selenium Transport in Hashimoto’s Thyroiditis

The essential trace element selenium (Se) is needed for the biosynthesis of selenocysteine-containing selenoproteins, including the secreted enzyme glutathione peroxidase 3 (GPX3) and the Se-transporter selenoprotein P (SELENOP). Both are found in blood and thyroid colloid, where they serve protective functions. Serum SELENOP derives mainly from hepatocytes, whereas the kidney contributes most serum GPX3. Studies using transgenic mice indicated that renal GPX3 biosynthesis depends on Se supply by hepatic SELENOP, which is produced in protein variants with varying Se contents. Low Se status is an established risk factor for autoimmune thyroid disease, and thyroid autoimmunity generates novel autoantigens. We hypothesized that natural autoantibodies to SELENOP are prevalent in thyroid patients, impair Se transport, and negatively affect GPX3 biosynthesis. Using a newly established quantitative immunoassay, SELENOP autoantibodies were particularly prevalent in Hashimoto’s thyroiditis as compared with healthy control subjects (6.6% versus 0.3%). Serum samples rich in SELENOP autoantibodies displayed relatively high total Se and SELENOP concentrations in comparison with autoantibody-negative samples ([Se]; 85.3 vs. 77.1 µg/L, p = 0.0178, and [SELENOP]; 5.1 vs. 3.5 mg/L, p = 0.001), while GPX3 activity was low and correlated inversely to SELENOP autoantibody concentrations. In renal cells in culture, antibodies to SELENOP inhibited Se uptake. Our results indicate an impairment of SELENOP-dependent Se transport by natural SELENOP autoantibodies, suggesting that the characterization of health risk from Se deficiency may need to include autoimmunity to SELENOP as additional biomarker of Se status.     

Novel Insights into Anthocyanin Metabolism and Molecular Characterization of Associated Genes in Sugarcane Rinds Using the Metabolome and Transcriptome

Saccharum officinarum (sugarcane) is the fifth major cultivated crop around the world. Sugarcane rind is a promising source for anthocyanin pigments; however, limited information is available on the anthocyanin and its biosynthesis in sugarcane rinds. In this study, we have quantified 49 compounds including 6 flavonoids and 43 anthocyanins in the rind of 6 sugarcane cultivars by using LCMS/MS approach. Thirty of them were quantified for the first time in sugarcane. The 43 anthocyanins included 10 cyanidin (Cya), 11 pelargonidin (Pel), 9 peonidin (Peo), 5 malvidin (Mal), 4 delphinidin (Del), and 4 petunidin (Pet) metabolites. High contents of Cya derivatives were observed in the rind of YT71/210 (dark purple rind), such as cya-3-O-(6-O-malonyl)-glu 1283.3 µg/g and cya-3-O-glu 482.67 µg/g followed by ROC22 (red rind) 821.3 µg/g and 409 µg/g, respectively, whereas the YT93/159 (green rind) showed a minimum level of these compounds. Among six cultivars, ROC22 rind has high levels of Peo derivatives such as peo-3-O-glu (197 µg/g), peo-3-O-(6-O-malonyl)-glu (69 µg/g) and peo-3-O-(6-O-p-coumaryl)-glu (55.17 µg/g). The gene expression analysis revealed that some genes, including a MYB(t) gene, were highly associated with the color phenotype. Thus, we cloned and overexpressed the gene in Arabidopsis and found the pinkish brown color in the hypocotyl of all transgenic lines compared with the wild type. Hence, we have quantified a wide range of anthocyanins in major sugarcane cultivars, reported many new anthocyanins for the first time, and concluded that Cya and Peo derivatives are the major contributing factor of dissimilar colors in sugarcane. The finding and the verification of a novel MYB gene involved in anthocyanin biosynthesis have demonstrated that our study was very valuable for gene discovery and genetic improvement of sugarcane cultivars to harvest high anthocyanin contents.     

An Insight into Anti-Inflammatory Activities and Inflammation Related Diseases of Anthocyanins: A Review of Both In Vivo and In Vitro Investigations

Anthocyanin is a type of flavonoid pigment widely present in fruits and vegetables. It can not only be used as natural pigment, but also has a variety of health functions, for instance, anti-oxidant, anti-inflammatory, anti-tumor, and neuroprotective activities. Persistent proinflammatory status is a major factor in the development, progression, and complications of chronic diseases. Not surprisingly, there are thus many food ingredients that can potentially affect inflammation related diseases and many studies have shown that anthocyanins play an important role in inflammatory pathways. In this paper, the inflammation related diseases (such as, obesity, diabetes, cardiovascular disease, and cancer) of anthocyanins are introduced, and the anti-inflammatory effect of anthocyanins is emphatically introduced. Moreover, the anti-inflammatory mechanism of anthocyanins is elaborated from the aspects of NF-κB, toll like receptor, MAPKs, NO, and ROS and the main efficacy of anthocyanins in inflammation and related diseases is determined. In conclusion, this review aims to get a clear insight into the role of anthocyanins in inflammation related diseases.     

Effects of Cynaroside on Cell Proliferation,Apoptosis, Migration and Invasion though the MET/AKT/mTOR Axis in Gastric Cancer

The Chinese medicine monomer cynaroside (Cy) is a flavonoid glycoside compound that widely exists in plants and has a variety of pharmacological effects, such as its important role in the respiratory system, cardiovascular system and central nervous system. Studies have reported that Cy has varying degrees of anticancer activity in non-small cell lung cancer, cervical cancer, liver cancer, esophageal cancer and other cancers. However, there are no relevant reports about its role in gastric cancer. The MET/AKT/mTOR signaling pathway plays important roles in regulating various biological processes, including cell proliferation, apoptosis, autophagy, invasion and tumorigenesis. In this study, we confirmed that Cy can inhibit the cell growth, migration and invasion and tumorigenesis in gastric cancer. Our finding shows that Cy can block the MET/AKT/mTOR axis by decreasing the phosphorylation level of AKT, mTOR and P70S6K. Therefore, the MET/AKT/mTOR axis may be an important target for Cy. In summary, Cy has anti-cancer properties and is expected to be a potential drug for the treatment of gastric cancer.     

Enzymatic Formation of Oxygen‐Containing Heterocycles in Natural Product Biosynthesis

Oxygen‐containing heterocycles are widely encountered in natural products that display diverse pharmacological properties and have potential benefits to human health. The formation of O‐heterocycles catalyzed by different types of enzymes in the biosynthesis of natural products not only contributes to the structural diversity of these compounds, but also enriches our understanding of nature's ability to construct complex molecules. This minireview focuses on the various modes of enzymatic O‐heterocyclization identified in natural product biosynthesis and summarizes the possible mechanisms involved in ring closure.     

Content and Color Stability of Anthocyanins Isolated from Schisandra chinensis Fruit

In this work, a multivariate study based on Box-Behnken Design was used to evaluate the influence of three major variables affecting the performance of the extraction process of Schisandra chinensis anthocyanins. The optimum parameters were 5.5 h extraction time; 1:19 solid-liquid ratio and 260 r/min stirring rate, respectively. The extraction yield of anthocyanins was 29.06 mg/g under the optimum conditions. Moreover, many factors on the impact of heating, ultrasound, microwave treatment and ultraviolet irradiation on content and color stability of anthocyanins from Schisandra chinensis fruit were investigated. The results show that thermal degradation reaction of anthocyanins complies with the first order reaction kinetics, and the correlation coefficient is greater than 0.9950 at 40–80 °C. Ultrasound and microwave treatment has little effect on the stability of anthocyanins, and the extraction time of ultrasound and microwave should be no more than 60 min and 5 min, respectively. The anthocyanins degradation effect of UVC ultraviolet radiation is greater than UVA and UVB; after 9 h ultraviolet radiation, the anthocyanins content degradation of UVC is 23.9 ± 0.7%, and the ΔE* was changed from 62.81 to 76.52 ± 2.3. Through LC-MS analysis, the major composition of Schisandra chinensis anthocyanins was cyanidin-3-O-xylosylrutinoside.     

The Role of Anthocyanins,Deoxyanthocyanins and Pyranoanthocyanins on the Modulation of Tyrosinase Activity: An In Vitro and In Silico Approach

Tyrosinase is the central enzyme involved in the highly complex process of melanin formation, catalyzing the rate-limiting steps of this biosynthetic pathway. Due to such a preponderant role, it has become a major target in the treatment of undesired skin pigmentation conditions and also in the prevention of enzymatic food browning. Numerous phenolic-based structures from natural sources have been pointed out as potential tyrosinase inhibitors, including anthocyanins. The aim of the present study was to individually assess the tyrosinase inhibitory activity of eight purified compounds with a variable degree of structural complexity: native anthocyanins, deoxyanthocyanins, and pyranoanthocyanins. The latter two, the groups of anthocyanin-related compounds with enhanced stability, were tested for the first time. Compounds 1 to 4 (luteolinidin, deoxymalvidin, cyanidin-, and malvidin-3-O-glucoside) revealed to be the most effective inhibitors, and further kinetic studies suggested their inhibition mechanism to be of a competitive nature. Structure–activity relationships were proposed based on molecular docking studies conducted with mushroom tyrosinase (mTYR) and human tyrosinase-related protein 1 (hTYRP1) crystal structures, providing information about the binding affinity and the different types of interactions established with the enzyme’s active center which corroborated the findings of the inhibition and kinetic studies. Overall, these results support the applicability of these compounds as pigmentation modulators.     

Spray-Drying Microencapsulation of Anthocyanins by Natural Biopolymers: A Review

There has been an increased interest in the development of food colorants from natural sources as alternatives to synthetic dyes because of both legislative actions and consumer concerns. Anthocyanins are of great interest for the food industry since they give a wide range of colors as well as nutraceutical activities. Nevertheless, due to their low stability to environmental conditions during processing and storage, introducing those compounds into foods is challenging. Microencapsulation may be an efficient way to introduce such compounds into those products. An important step in developing microcapsules is the selection of a biopolymer (wall material) which meets the required criteria. Hence, this review will focus on microencapsulation of anthocyanins with different biopolymers through spray drying to develop natural colorant pigments which possess high stability, solubility, and dispersibility. Our goal is to give updated information regarding microencapsulation of anthocyanins by spray drying, as well as its effectiveness, developments, and optimized conditions which will be discussed.