Engineered Neutral Phosphorous Dendrimers Protect Mouse Cortical Neurons and Brain Organoids from Excitotoxic Death

Nanoparticles are playing an increasing role in biomedical applications. Excitotoxicity plays a significant role in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s or Parkinson’s disease. Glutamate ionotropic receptors, mainly those activated by N-methyl-D-aspartate (NMDA), play a key role in excitotoxic death by increasing intraneuronal calcium levels; triggering mitochondrial potential collapse; increasing free radicals; activating caspases 3, 9, and 12; and inducing endoplasmic reticulum stress. Neutral phosphorous dendrimers, acting intracellularly, have neuroprotective actions by interfering with NMDA-mediated excitotoxic mechanisms in rat cortical neurons. In addition, phosphorous dendrimers can access neurons inside human brain organoids, complex tridimensional structures that replicate a significant number of properties of the human brain, to interfere with NMDA-induced mechanisms of neuronal death. Phosphorous dendrimers are one of the few nanoparticles able to gain access to the inside of neurons, both in primary cultures and in brain organoids, and to exert pharmacological actions by themselves.     

The anticarcinogenic potential of essential oil and aqueous infusion from caper (Capparis spinosa L.)

The present study assessed the influence of essential oil and aqueous infusion from wild-grown caper (Capparis spinosa L.) on cell growth, NF-κB activation, apoptosis and cell cycle in the human colon carcinoma cell line, HT-29. Methyl isothiocyanate (92.06%), a degradation product of glucosinolate glucocapparin, was detected as major component of essential oil from caper leaves and flower buds. Aqueous infusion of caper showed an interesting and variegate compositional pattern containing several phenolic compounds, among which a flavonol glycoside, rutin (quercetin 3-O-rutinoside, 50.7%) and 5-caffeoyl-quinic acid (chlorogenic acid, 17.5%) were detected as dominant. Caper essential oil and aqueous infusion showed time- and dose-dependent high inhibitory effect on HT-29 cell proliferation. In addition, they induced the inhibition on nuclear factor κB (NF-κB) activity in a dose-dependent manner, while they did not show any effect on apoptosis in HT-29 cells. Flow cytometric analysis indicated that treatment with caper essential oil and aqueous infusion resulted in G₂/M cell cycle arrest in a dose-dependent manner. Presented results suggest that caper contains volatile and non-volatile compounds which potentially can play an important role in colon cancer prevention.     

Determination of polyphenolic content and antioxidant activity of kudingcha made from Ilex kudingcha C.J. Tseng

The total polyphenol content and the antioxidant activity of kudingcha made from Ilex kudingcha C.J. Tseng were determined by Folin–Ciocalteu reagent, and DPPH, FRAP, and TEAC methods, respectively. The crude extract (CE) of kudingcha and its four fractions of chloroform (CfF), ethyl acetate (EaF), n-butanol (nBF), and water (WtF) were prepared and subjected to antioxidant evaluation and analysis by high performance liquid chromatography. The extracts of kudingcha contained large amounts of caffeoylquinic acid (CQA) derivatives, including 3-CQA, 5-CQA, 3,4-diCQA, 3,5-diCQA, and 4,5-diCQA, and showed potent antioxidant activity. The antioxidant activities of CE and its fractions decreased in the order of EaF > nBF > CE > WtF > CfF, according to the DPPH assay and FRAP assay, which were the same, with the exception of the rank order of CfF and WtF, as the TEAC assay. Furthermore, a satisfactory correlation between total polyphenol content and antioxidant activity was observed.     

Intracellular silver accumulation in Chlamydomonas reinhardtii upon exposure to carbonate coated silver nanoparticles and silver nitrate

The intracellular silver accumulation ({Ag}(in)) upon exposure to carbonate coated silver nanoparticles (AgNP, 0.5-10 μM, average diameter 29 nm) and silver nitrate (20-500 nM) was examined in the wild type and in the cell wall free mutant of the green alga Chlamydomonas reinhardtii at pH 7.5. The {Ag}(in) was measured over time up to 1 h after a wash procedure to remove silver ions (Ag(+)) and AgNP from the algal cell surface. The {Ag}(in) increased with increasing exposure time and with increasing AgNP and AgNO(3) concentrations in the exposure media, reaching steady-state concentrations between 10(-5) and 10(-3) mol L(cell)(-1). According to estimated kinetic parameters, high Ag(+) bioconcentration factors were calculated (>10(3) L L(cell)(-1)). Higher accumulation rate constants were assessed in the cell wall free mutant, indicating a protective role of the cell wall in limiting Ag(+) uptake. The bioavailability of AgNP was calculated to be low in both strains relative to Ag(+), suggesting that AgNP internalization across the cell membrane was limited.     

Application of Fast Gas Chromatography–Mass Spectrometry in Combination with the QuEChERS Method for the Determination of Pesticide Residues in Fruits and Vegetables

A fast gas chromatography–mass spectrometry method has been developed for multiresidue determination of up to 56 pesticides in fruits and vegetables in a chromatographic run time of <10 min, using a single quadrupole mass spectrometer operating in selected ion monitoring mode. The well-known acetate-buffering version of the QuEChERS method has been used for sample preparation. Programmable temperature vaporizer injection of 3 μL allowed reaching limits of detection between 0.15 and 15 μg/kg for most compounds in the sample matrices tested. The applicability of the method has been evaluated in apple, orange, carrot, and tomato. Recoveries at three fortification levels (0.01, 0.1 and 0.5 mg/kg) ranged from 70 to 120 % for most compounds, with relative standard deviations below 20 % in all cases. The developed method has been applied to fruit and vegetable samples from different Spanish provinces.     

Use of ionic liquids based on phosphonium salts for preparing biocomposites by in situ polymerization

A sodium montmorillonite, Dellite HPS, was modified with ionic liquids based on phosphonium salts, such as octadecyltriphenylphosphonium tetrafluoroborate and octadecyltriphenylphosphonium bromide. Thanks to their high thermal stability, these salts can be used during in situ polymerization, a method that favors the achievement of a good dispersion of the clay. Poly(1,4‐dimethylcyclohexane adipate) (PCHA), was chosen as an example of aliphatic polyester which can be a suitable matrix for new biocomposites with organo‐clays. The organo modified clays prepared were characterized by X‐ray diffraction (XRD), ATR‐FTIR spectroscopy, and thermal gravimetric analysis (TGA) while biocomposites were analyzed in terms of molecular structure, thermal and thermomechanical properties. The degree of dispersion of the clays in the polymer matrix was studied by XRD. The results show that the clays are well dispersed in the biocomposites, despite an intercalated structure highlighted by XRD analysis. Moreover, the clays confer a certain improvement in mechanical properties to the final materials. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42467.     

Novel Tacrine‐Grafted Ugi Adducts as Multipotent Anti‐Alzheimer Drugs: A Synthetic Renewal in Tacrine–Ferulic Acid Hybrids

Herein we describe the design, multicomponent synthesis, and biological, molecular modeling and ADMET studies, as well as in vitro PAMPA‐blood–brain barrier (BBB) analysis of new tacrine–ferulic acid hybrids (TFAHs). We identified (E)‐3‐(hydroxy‐3‐methoxyphenyl)‐N‐{8[(7‐methoxy‐1,2,3,4‐tetrahydroacridin‐9‐yl)amino]octyl}‐N‐[2‐(naphthalen‐2‐ylamino)2‐oxoethyl]acrylamide (TFAH 10 n ) as a particularly interesting multipotent compound that shows moderate and completely selective inhibition of human butyrylcholinesterase (IC₅₀=68.2 nM ), strong antioxidant activity (4.29 equiv trolox in an oxygen radical absorbance capacity (ORAC) assay), and good β‐amyloid (Aβ) anti‐aggregation properties (65.6 % at 1:1 ratio); moreover, it is able to permeate central nervous system (CNS) tissues, as determined by PAMPA‐BBB assay. Notably, even when tested at very high concentrations, TFAH 10 n easily surpasses the other TFAHs in hepatotoxicity profiling (59.4 % cell viability at 1000 μM ), affording good neuroprotection against toxic insults such as Aβ_1–40, Aβ_1–42, H₂O₂, and oligomycin A/rotenone on SH‐SY5Y cells, at 1 μM . The results reported herein support the development of new multipotent TFAH derivatives as potential drugs for the treatment of Alzheimer′s disease.     

Gender and dietary fat affect α-tocopherol status in F344/N rats

For four weeks, groups of eight male and eight female F344/N rats were fed diets containing 15.5, 20, 30 or 40% of energy (en%) as fat. The fat was composed of corn oil and beef tallow with 9 en% from linoleate in all diets. Females had greater mean hepatic α-tocopherol levels, whereas males had greater plasma α-tocopherol and cholesterol concentrations. In males, the plasma ratio of α-tocopherol/cholesterol was significantly greater than in females (P<0.05). Plasma α-tocopherol increased with increasing en% fat (r=0.51,P<0.001) in both sexes, but dietary fat did not alter hepatic α-tocopherol levels. These results suggest that plasma α-tocopherol may serve as a biomarker of total dietary fat intake and that in F344/N rats gender differences affect α-tocopherol and cholesterol status.