In vitro β‐Carotene Bioaccessibility and Lipid Digestion in Emulsions: Influence of Pectin Type and Degree of Methyl‐Esterification

Citrus pectin (CP) and sugar beet pectin (SBP) were demethoxylated and fully characterized in terms of pectin properties in order to investigate the influence of the pectin degree of methyl‐esterification (DM) and the pectin type on the in vitro β‐carotene bioaccessibility and lipid digestion in emulsions. For the CP based emulsions containing β‐carotene enriched oil, water and pectin, the β‐carotene bioaccessibility, and lipid digestion were higher in the emulsions with pectin with a higher DM (57%; “CP57 emulsion”) compared to the emulsions with pectin with a lower DM (30%; “CP30 emulsion”) showing that the DM plays an important role. In contrast, in SBP‐based emulsions, nor β‐carotene bioaccessibility nor lipid digestion were dependent on pectin DM. Probably here, other pectin properties are more important factors. It was observed that β‐carotene bioaccessibility and lipid digestion were lower in the CP30 emulsion in comparison with the CP57, SBP32, and SBP58 emulsions. However, the β‐carotene bioaccessibility of CP57 emulsion was similar to that of the SBP emulsions, whereas the lipid digestion was not. It seems that pectin type and pectin DM (in case of CP) are determining which components can be incorporated into micelles. Because carotenoids and lipids have different structures and polarities, their incorporation may be different. This knowledge can be used to engineer targeted (digestive) functionalities in food products. If both high β‐carotene bioaccessibility and high lipid digestion are targeted, SBP emulsions are the best options. The CP57 emulsion can be chosen if high β‐carotene bioaccessibility but lower lipid digestion is desired.     

Investigating Biomarkers for USH2A Retinopathy Using Multimodal Retinal Imaging

Pathogenic mutations in USH2A are a leading cause of visual loss secondary to non-syndromic or Usher syndrome-associated retinitis pigmentosa (RP). With an increasing number of RP-targeted clinical trials in progress, we sought to evaluate the photoreceptor topography underlying patterns of loss observed on clinical retinal imaging to guide surrogate endpoint selection in USH2A retinopathy. In this prospective cross-sectional study, twenty-five patients with molecularly confirmed USH2A-RP underwent fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO) retinal imaging. Analysis comprised measurement of FAF horizontal inner (IR) and outer (OR) hyperautofluorescent ring diameter; SD-OCT ellipsoid zone (EZ) and external limiting membrane (ELM) width, normalised EZ reflectance; AOSLO foveal cone density and intact macular photoreceptor mosaic (IMPM) diameter. Thirty-two eyes from 16 patients (mean age ± SD, 36.0 ± 14.2 years) with USH2A-associated Usher syndrome type 2 (n = 14) or non-syndromic RP (n = 2) met the inclusion criteria. Spatial alignment was observed between IR-EZ and OR-ELM diameters/widths (p < 0.001). The IMPM border occurred just lateral to EZ loss (p < 0.001), although sparser intact photoreceptor inner segments were detected until ELM disruption. EZ width and IR diameter displayed a biphasic relationship with cone density whereby slow cone loss occurred until retinal degeneration reached ~1350 μm from the fovea, beyond which greater reduction in cone density followed. Normalised EZ reflectance and cone density were significantly associated (p < 0.001). As the strongest correlate of cone density (p < 0.001) and best-corrected visual acuity (p < 0.001), EZ width is the most sensitive biomarker of structural and functional decline in USH2A retinopathy, rendering it a promising trial endpoint.     

Dietary fat and breast cancer mortality: A systematic review and meta-analysis

Background: The influence of dietary fat upon breast cancer mortality remains largely understudied despite extensive investigation into its influence upon breast cancer risk. Objective: To conduct meta-analyses of studies to clarify the association between dietary fat and breast cancer mortality. Design: MEDLINE and EMBASE were searched for relevant articles published up to March 2012. Risk of all-cause or breast-cancer-specific death was evaluated by combining multivariable adjusted estimates comparing highest versus lowest categories of intake; and per 20 g increase in intake of total and/or saturated fat (g/day) using random-effects meta-analyses. Results: Fifteen prospective cohort studies investigating total fat and/or saturated fat intake (g/day) and breast cancer mortality were included. There was no difference in risk of breast-cancer-specific death (n = 6; HR = 1.14; 95% CI: 0.86, 1.52; p = 0.34) or all-cause death (n = 4; HR = 1.73; 95% CI: 0.82, 3.66; p = 0.15) for women in the highest versus lowest category of total fat intake. Breast-cancer-specific death (n = 4; HR = 1.51; 95% CI: 1.09, 2.09; p < 0.01) was higher for women in the highest versus lowest category of saturated fat intake. Conclusions: These meta-analyses have shown that saturated fat intake negatively impacts upon breast cancer survival.     

Antimicrobial peptides and pregnancy

Antimicrobial peptides (AMPs) are small proteins produced by epithelial surfaces and inflammatory cells, which have broad-spectrum antimicrobial and immunomodulatory activities. They are known to be important in a number of infectious and inflammatory conditions and have been shown to be present in a number of sites throughout the female reproductive tract. Inflammation and infection are associated with a number of complications of pregnancy including preterm labor, and AMPs may play a key role in maintaining and protecting pregnancy. The aim of this review is to describe the expression and function of AMPs in the pregnant female reproductive tract and their relation to preterm labor.     

Interior-architectured ZnO nanostructure for enhanced electrical conductivity via stepwise fabrication process

Fabrication of ZnO nanostructure via direct patterning based on sol-gel process has advantages of low-cost, vacuum-free, and rapid process and producibility on flexible or non-uniform substrates. Recently, it has been applied in light-emitting devices and advanced nanopatterning. However, application as an electrically conducting layer processed at low temperature has been limited by its high resistivity due to interior structure. In this paper, we report interior-architecturing of sol-gel-based ZnO nanostructure for the enhanced electrical conductivity. Stepwise fabrication process combining the nanoimprint lithography (NIL) process with an additional growth process was newly applied. Changes in morphology, interior structure, and electrical characteristics of the fabricated ZnO nanolines were analyzed. It was shown that filling structural voids in ZnO nanolines with nanocrystalline ZnO contributed to reducing electrical resistivity. Both rigid and flexible substrates were adopted for the device implementation, and the robustness of ZnO nanostructure on flexible substrate was verified. Interior-architecturing of ZnO nanostructure lends itself well to the tunability of morphological, electrical, and optical characteristics of nanopatterned inorganic materials with the large-area, low-cost, and low-temperature producibility.     

Mycotoxin Biomarkers of Exposure: A Comprehensive Review

To date, the use of biomarkers has become generally accepted. Biomarker‐driven research has been proposed as a successful method to assess the exposure to xenobiotics by using concentrations of the parent compounds and/or metabolites in biological matrices such as urine or blood. However, the identification and validation of biomarkers of exposure remain a challenge. Recent advances in high‐resolution mass spectrometry along with new analytical (post‐acquisition data‐mining) techniques will improve the quality and output of the biomarker identification process. Chronic or even acute exposure to mycotoxins remains a daily fact, and therefore it is crucial that the mycotoxins’ metabolism is unravelled so more knowledge on biomarkers in humans and animals is acquired. This review aims to provide the scientific community with a comprehensive overview of reported in vitro and in vivo mycotoxin metabolism studies in relation to biomarkers of exposure for deoxynivalenol, nivalenol, fusarenon‐X, T‐2 toxin, diacetoxyscirpenol, ochratoxin A, citrinin, fumonisins, zearalenone, aflatoxins, and sterigmatocystin.     

Quinone emissions from gasoline and diesel motor vehicles

Gas- and particle-phase emissions from gasoline and diesel vehicles operated on chassis dynamometers were collected using annular denuders, quartz filters, and PUF substrates. Quinone species were measured using O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine derivatization in conjunction with gas chromatography-mass spectrometry and high-performance liquid chromatography-mass spectrometry. Nine quinones were observed, ranging from C6 to C16. New species identified in motor vehicle exhaust include methyl-1,4-benzoquinone, 2-methyl-1,4-naphthoquinone (MNQN), and aceanthrenequinone. Gas-phase motor vehicle emissions of quinones are also reported for the first time. Six gas-phase quinones were quantified with emission rates of 2-28 000 microg L(-1) fuel consumed. The most abundant gas-phase quinones were 1,4-benzoquinone (BON) and MNQN. The gas-phase fraction was > or = 69% of quinone mass for light-duty gasoline emissions, and > or = 84% for heavy-duty diesel emissions. Eight particle-phase quinones were observed between 2 and 1600 microg L(-1), with BQN the most abundant species followed by 9,10-phenanthrenequinone and 1,2-naphthoquinone. Current particle-phase quinone measurements agree well with the few available previous results. Further research is needed concerning the gas-particle partitioning behavior of quinones in ambient and combustion source conditions.     

Proteome profiling of exosomes derived from plasma of heifers with divergent genetic merit for fertility

The current study evaluated exosomes isolated from plasma of heifers bred to have high or low fertility through developing extreme diversity in fertility breeding values, however, key animal traits (e.g., body weight, milk production, and percentage of North American genetics) remained similar between the 2 groups. The exosomes were isolated by a combined ultracentrifugation and size exclusion chromatography approach and characterized by their size distribution (nanoparticle tracking analysis), morphology (transmission electron microscopy), and presence of exosomal markers (immunoblotting). In addition, a targeted mass spectrometry approach was used to confirm the presence of 2 exosomal markers, tumor susceptibility gene 101 and flotillin 1. The number of exosomes from plasma of high fertility heifers was greater compared with low fertility heifers. Interestingly, the exosomal proteomic profile, evaluated using mass spectrometry, identified 89 and 116 proteins in the high and low fertility heifers respectively, of which 4 and 31 were unique, respectively. These include proteins associated with specific biological processes and molecular functions of fertility. Most notably, the tetratricopeptide repeat protein 41-related, glycodelin, and kelch-like protein 8 were identified in plasma exosomes unique to the low fertility heifers. These proteins are suggested to play a role in reproduction; however, the role of these proteins in dairy cow reproduction remains to be elucidated. Their identification underscores the potential for proteins within exosomes to provide information on the fertility status and physiological condition of the cow. This may potentially lead to the development of prognostic tools and interventions to improving dairy cow fertility.     

Inhibition of Toll-Like Receptor 4 Signaling Mitigates Microvascular Loss but Not Fibrosis in a Model of Ischemic Acute Kidney Injury

The development of chronic kidney disease (CKD) following an episode of acute kidney injury (AKI) is an increasingly recognized clinical problem. Inhibition of toll-like receptor 4 (TLR4) protects renal function in animal models of AKI and has become a viable therapeutic strategy in AKI. However, the impact of TLR4 inhibition on the chronic sequelae of AKI is unknown. Consequently, we examined the chronic effects of TLR4 inhibition in a model of ischemic AKI. Mice with a TLR4-deletion on a C57BL/6 background and wild-type (WT) background control mice (C57BL/6) were subjected to bilateral renal artery clamping for 19 min and reperfusion for up to 6 weeks. Despite the acute protective effect of TLR4 inhibition on renal function (serum creatinine 1.6 ± 0.4 mg/dL TLR4-deletion vs. 2.8 ± 0.3 mg/dL·WT) and rates of tubular apoptosis following ischemic AKI, we found no difference in neutrophil or macrophage infiltration. Furthermore, we observed significant protection from microvascular rarefaction at six weeks following injury with TLR4-deletion, but this did not alter development of fibrosis. In conclusion, we validate the acute protective effect of TLR4 signal inhibition in AKI but demonstrate that this protective effect does not mitigate the sequential fibrogenic response in this model of ischemic AKI.     

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.