Silica-templated photonic crystal sensors for specific detection of Cu2.

Responsive photonic crystals have attracted extensive attention due to their features of transforming external stimuli into a variation of optical signals or structural colors. In recent years, the accumulation of heavy metal ions has become a serious threat to human health and the environment. Thus, a simple and rapid method for the accurate detection of metal ions is of great importance. Herein, an imidazole-based-silica inverse opal photonic crystal (IOPC) sensor is prepared. Three different particle sizes of SiO2 photonic crystals were used as templates for the preparation of an IOPC. The results show that the template presents a high specific surface area and interconnected nanopores. When the nanopores adsorb copper ions, the functional monomer imidazole will chelate with copper ions to form a flat quadrilateral structure. Then the nanopores of the IOPC shrink, which will result in the red shifting of the diffraction peak to complete the visual response sensing. When immersed in different concentrations of metal ions, the structural color of the IOPC changes, making it a visual sensor. In addition, it is proved that the imidazole-modified IOPC is specifically responsive to Cu2+, and the structural color of the sensor will shift from green to yellow after sensing. The detection limit is as low as 1 × 10-6 mol L-1, and the maximum offset of the diffraction peak can reach 50 nm. Therefore, the IOPC prepared here provides an ideal platform for the fast and high selective detection of Cu2+, and it has potential applications in the rapid detection of other heavy metal ions.

Oat polyphenol avenanthramide-2c confers protection from oxidative stress by regulating the Nrf2-ARE signaling pathway in PC12 cells.

Accumulating evidence has demonstrated that cellular antioxidant systems play essential roles in retarding oxidative stress-related diseases, such as Parkinson's disease. Because nuclear factor erythroid 2-related factor 2 (Nrf2) is a chief regulator of cellular antioxidant systems, small molecules with Nrf2-activating ability may be promising neuroprotective agents. Avenanthramide-2c (Aven-2c), avenanthramide-2f (Aven-2f) and avenanthramide-2p (Aven-2p) are the most abundant avenanthramides in oats, and they have been documented to possess multiple pharmacological benefits. In this work, we synthesized these three compounds and evaluated their cytoprotective effect against oxidative stress-induced PC12 cell injuries. Aven-2c displayed the best protective potency among them. Aven-2c conferred protection on PC12 cells by scavenging free radicals and activating the Nrf2-ARE signaling pathway. Pretreatment of PC12 cells with Aven-2c efficiently enhanced Nrf2 nuclear accumulation and evoked the expression of a set of cytoprotective molecules. The mechanistic study also supports that Nrf2 activation is the molecular basis for the cellular action of Aven-2c. Collectively, this study demonstrates that Aven-2c is a potent Nrf2 agonist, shedding light on the potential usage of Aven-2c in the treatment of neuroprotective diseases.

Generation of potent Nrf2 activators via tuning the electrophilicity and steric hindrance of vinyl sulfones for neuroprotection.

Oxidative stress is constantly involved in the etiopathogenesis of an ever-widening range of neurodegenerative diseases. As a consequence, effective repression of cellular oxidative stress to a redox homeostatic condition is a promising and feasible strategy to treat, or at least retard the progression of, such disorders. Nrf2, a primary orchestrator of cellular antioxidant response machine, is responsible for detoxifying and compensating for deleterious oxidative stress via transcriptional activation of a diverse array of antioxidant biomolecules. In the framework of our persistent interest in disclosing small molecules that interfere with cellular redox-regulating machinery, we report herein the synthesis, optimization, and biological assessment of 47 vinyl sulfone scaffold-bearing small molecules, most of which exhibit robust neuroprotective effect against H2O2-mediated lesions to PC12 cells. After initial screening, the most potent neuroprotective compounds 9b and 9c with marginal cytotoxicity were selected for the follow-up studies. Our results demonstrate that their neuroprotective effects are attributed to the up-regulation of a panel of antioxidant genes and corresponding gene products. Further mechanistic studies indicate that Nrf2 is indispensable for the cellular performances of 9b and 9c, arising from the fact that silence of Nrf2 gene drastically nullifies their protective action. Taken together, 9b and 9c discovered in this work merit further development as neuroprotective candidates for the treatment of oxidative stress-mediated pathological conditions.

A ß-allyl carbamate fluorescent probe for vicinal dithiol proteins.

The first ß-allyl carbamate fluorescent probe, AC-green, was reported for specifically imaging vicinal dithiol proteins (VDPs) in living systems. The probe displays low toxicity and features high sensitivity and fast response towards VDPs. A drastic loss of VDPs in a Parkinson's model was disclosed by AC-green, linking the fluctuation of VDP levels to Parkinson's disease for the first time. The structural novelty and favorable properties of AC-green will advance the development of novel VDP probes.

Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes.

Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine- or H2O2-induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.

Lipoamide Ameliorates Oxidative Stress via Induction of Nrf2/ARE Signaling Pathway in PC12 Cells.

The mechanisms underlying neurodegenerative diseases are not fully understood yet. However, an increasing amount of evidence has suggested that these disorders are related to oxidative stress. We reported herein that lipoamide (LM), a neutral amide derivative of lipoic acid (LA), could resist oxidative stress-mediated neuronal cell damage. LM is more potent than LA in alleviating hydrogen peroxide- or 6-hydroxydopamine-induced PC12 cell injury. Our results reveal that LM promotes the nuclear accumulation of NFE2-related factor 2 (Nrf2), following with the activation of expression of Nrf2-governed antioxidant and detoxifying enzymes. Notably, silencing Nrf2 gene annuls the protection of LM, which demonstrates that Nrf2 is engaged in this cytoprotection. Our findings suggest that LM might be used as a potential therapeutic candidate for oxidative stress-related neurological disorders.

An Azo Coupling Strategy for Protein 3-Nitrotyrosine Derivatization.

Herein, a strategy for the selective derivatization of 3-nitrotyrosine-containing proteins using the classic azo coupling reaction as the key step is described. This novel approach featured multiple advantages and was successfully applied to detect picomole levels of protein tyrosine nitration in biological samples.

Xanthohumol Analogues as Potent Nrf2 Activators against Oxidative Stress Mediated Damages of PC12 Cells.

The nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcription factor controlling a series of cytoprotective genes, is closely associated with scavenging the reactive oxygen species and maintaining the intracellular redox balance. Accumulating evidence has indicated that activation of Nrf2 is efficient to block or retard oxidative stress mediated neurodegenerative disorders. Small molecules that contribute directly or indirectly to the Nrf2 activation thus are promising therapeutic agents. Herein, we screened xanthohumol and its analogues, and two analogues (11 and 12) were disclosed to possess low cytotoxicity and rescue PC12 cells from the hydrogen peroxide or 6-hydroxydopamine induced injuries. Molecular mechanism studies demonstrated that compounds 11 and 12 are potent Nrf2 activators by promoting the nuclear accumulation of Nrf2 and enhancing the cellular antioxidant defense system. More importantly, genetically silencing the Nrf2 expression shuts down the observed cytoprotection conferred by both compounds, supporting the critical involvement of Nrf2 for the cellular actions of compounds 11 and 12.

Development and evaluation of lutein-loaded alginate microspheres with improved stability and antioxidant.

BACKGROUND: Lutein has been of great interest to the food processing and pharmaconutrient industries owing to its beneficial effects on human health. However, lutein is very sensitive to heat, light, pH and oxidative conditions, which limits its application in food systems. The present study aimed to prepare lutein-alginate microspheres by a calcium chloride gelation method with the purpose of improving the stability and antioxidant abilities of lutein. RESULTS: The loading capacity of lutein in the microspheres was approximately 5.3% (w/w) and the entrapment efficiency was about 63%. The loaded microspheres were nearly spherical with an average size of 150 µm. They exhibited a crimped surface by scanning electron microscopy. The lutein was in amorphous state by X-ray powder diffraction. Analysis by Fourier transform infrared spectroscopy and molecular docking revealed an intermolecular hydrogen bond interaction between lutein and sodium alginate. In vitro release experiments showed that the microspheres presented slower release at acidic conditions than at neutral intestinal conditions. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of the microencapsulated lutein was higher than that of free lutein. The stability of lutein in the microspheres was improved significantly when compared with that of free lutein at various temperatures. CONCLUSION: The present work successfully developed well-protected lutein-alginate microspheres. This indicates that it is feasible to use microspheres loaded with lutein as antioxidant functional ingredients in food products. © 2019 Society of Chemical Industry.

Improved oral bioavailability of 20(R)-25-methoxyl-dammarane-3ß, 12ß, 20-triol using nanoemulsion based on phospholipid complex: design, characterization, and in vivo pharmacokinetics in rats.

The aim of the study was to improve the oral absorption of the compound 25-OCH3-PPD with poor hydrophilicity and lipophilicity. 25-OCH3-PPD-phospholipid complex was prepared by solvent evaporation, then characterized by differential scanning calorimetry, scanning electron microscopy, and infrared absorption spectroscopy. The aqueous solubility and oil-water partition coefficient were compared with the free compound. A nanoemulsion loaded with 25-OCH3-PPD-phospholipid complex was developed by dissolving the complex in water in the presence of hydrophilic surfactant under sonication. After oral administration of the nanoemulsion and the suspension of 25-OCH3-PPD in rats, the concentrations of 25-OCH3-PPD in plasma were determined by high-performance liquid chromatography-tandem mass spectrometry method. The results showed that the solubility of the complex in water and n-octanol was enhanced. The oil-water partition coefficient improved 1.7 times. Peak plasma concentration and area under the curve(0-24 h) of the nanoemulsion of 25-OCH3-PPD-phospholipid complex were higher than that of free compound by 3.9- and 3.5-folds.

Site-selective functionalization of periodic mesoporous organosilica (PMO) with macrocyclic host for specific and reversible recognition of heavy metal.

A novel kind of macrocyclic-host-functionalized periodic mesoporous organosilica (PMO) with excellent and reversible recognition of Pb(II) was developed. The macrocyclic host molecule cis-dicyclohexano[18]crown-6, with strong affinity to Pb(II), was carefully modified as a bridged precursor to build the PMO material. To break down the limit of the functionalization degree for PMOs incorporated with large-sized moieties, a site-selective post-functionalization method was proposed to further decorate the external surface of the PMO material. The selective recognition ability of the upgraded PMO material towards Pb(II) was remarkably enhanced without destroying the mesoporous ordering. Solid-state (13)C and (29)Si NMR spectroscopy, X-ray photoelectron spectroscopy (XPS), XRD, TEM, and nitrogen adsorption-desorption isotherm measurements were utilized for a full characterization of the structure, micromorphology, and surface properties. Reversible binding of Pb(II) was realized in the binding-elution cycle experiments. The mechanism of the supramolecular interaction between the macrocyclic host and metal ion was discussed. The synthetic strategy can be considered a general way to optimize the properties of PMOs as binding materials for practical use while preserving the mesostructure.

Novel polysiloxane resin functionalized with dicyclohexano-18-crown-6 (DCH18C6): Synthesis, characterization and extraction of Sr(II) in high acidity HNO3 medium.

A novel kind of polysiloxane resin functionalized with dicyclohexano-18-crown-6 (DCH18C6) was synthesized through a post-modification approach. The DCH18C6 moieties bearing amino groups were firstly prepared, followed by covalent grafting to a silica precursor P-(CH(2))(3)-Cl (Where P represents a 3-dimentional polymerized silica matrix) based on nucleophilic substitution reaction. (29)Si and (13)C solid-state NMR, FT-IR, XPS, TGA, ESEM and elemental analysis were employed to systematically characterize the structure, thermal property and surface morphology of the functionalized resin. The results indicated that the DCH18C6 ligands were successfully bonded to the polysiloxane resin with a satisfactory grafting degree (33.6wt.%). Due to the robust organosilica framework and the covalent immobilization of the ligands, the functionalized resin had excellent thermal stability and acid resistance. Batch experiments showed that the resin could effectively separate Sr(II) in high acidity mediums. The distribution coefficient (K(d)) of 43.6cm(3)/g could be achieved in 5.0mol/L HNO(3) solution. The influences of contact time and acidity of HNO(3) on the resin's extraction performance were examined. The reusability and the selectivity to Sr(II) over interference ions were investigated. The DCH18C6-functionalized resin might be potentially applied for the radiostrontium removal in the high level liquid waste (HLLW).