Myocardial infarction (MI) continues to be a major contributor to the morbidity and mortality across the globe. Injectable hydrogel, a tissue-engineered scaffold, recently demonstrated very promising in myocardial repair. However, the undesirable retention and survival of transplanted cells has limited their applications due to the oxidative stress microenvironment of MI lesions. In this work, a thermosensitive α-tocopherol (AT) liposome loaded chitosan hydrogel was developed to suppress the oxidative stress injury in cardiomyocytes. AT was embedded in the liposomes to improve its solubility and stability. The innovative AT liposome loaded chitosan hydrogel (AT-LCH) system had an appropriate sol-to-gel transition temperature. Hydrogels possessed a highly porous structure with irregular pores interconnected throughout the construct as shown by SEM, and liposomes distributed uniformly in the porous structure. A sustained AT release was observed in AT-LCH. In addition, AT-LCH has shown an excellent biocompatibility to support the adhesion and survival of cardiomyocytes. Moreover, it can resist the oxidative stress environment and improve the survival of cardiomyocytes. In general, this work suggests that AT-LCH may present an ideal scaffold material for injectable cardiac tissue engineering.

Oxidative stress is associated with adverse pregnancy outcomes, and vitamin E has powerful anti-oxidant properties with the potential to impact health outcomes. Tocopherol isomers of vitamin E differ in their ability to modulate inflammation and vary in concentration in diets containing high proportions of processed versus unprocessed foods. The purpose of this study was to compare vitamin E status and associated pregnancy outcomes (mode of delivery, chorioamnionitis, APGARs (measure of appearance, pulse, grimace, activity, respiration), gestational age at delivery, and fetal growth) between maternal⁻infant dyads in a developed and a developing nation to identify potentially modifiable differences that may impact pregnancy and neonatal outcomes and provide a way to improve maternal and neonatal health. Plasma tocopherol levels were evaluated in 189 Midwestern United States (US) mother⁻infant pairs and 99 Central Nigerian mother⁻infant pairs. Maternal and infant concentrations of α-, γ-, and δ-tocopherol were measured using HPLC with diode-array detection. Descriptive statistics were calculated and tocopherol concentrations were associated with clinical outcomes such as mode of delivery, chorioamnionitis, APGARS, and fetal growth. Alpha- and γ-tocopherol levels were higher in the US mothers, (alpha: 12,357.9 (175.23⁻34,687.75) vs. 8333.1 (1576.59⁻16,248.40) (mcg/L); p < 0.001) (gamma: 340.7 (224.59⁻4385.95) vs. 357.5 (66.36⁻1775.31) (mcg/L); p < 0.001), while δ-tocopherol levels were higher in the Nigerian mothers (delta: 261.7 (24.70⁻1324.71) vs. 368.9 (43.06⁻1886.47) (mcg/L); p < 0.001). US infants had higher γ-tocopherol levels than Nigerian infants (203.1 (42.53⁻1953.23) vs. 113.8 (0.00⁻823.00) (mcg/L); p < 0.001), while both the Nigerian mothers and infants had higher α:γ-tocopherol ratios (8.5 vs. 26.2, and 8.9 vs. 18.8, respectively; p < 0.001). Our results in both populations show associations between increased circulating γ-tocopherol and negative outcomes like Caesarian sections, in contrast to the associations with positive outcomes such as vaginal delivery seen with increased α:γ-tocopherol ratios. Growth was positively associated with α- and γ-tocopherols in cord blood in the US population, and with cord blood δ-tocopherols in the Nigerian population. Tocopherol levels likely impact health outcomes in pregnancy in a complicated metabolism across the maternal⁻fetal axis that appears to be potentially influenced by culture and available diet.

This study aimed at investigating the potential mechanism of improved transportation of the curcumin loaded D-α-tocopherol polyethylene glycol 1000 succinate coated nanodiamonds system (NDs/CUR/TPGS complexes) using an in vitro Caco-2 cell monolayer model. The core-shell structured NDs/CUR/TPGS nanocomplexes were 196.32 ± 5.76 nm in size, with a high loading efficiency of 81.59±3.42 %. Cytotoxicity results suggested that the blank NDs did not induce any serious toxicity on Caco-2 cells even after incubated for 72h. The cell viability for all the series of CUR loaded preparations was found to follow the sequence of CUR suspension > NDs/CUR > NDs/CUR/TPGS. Confocal laser fluorescence microscopy (CLSM) and flow cytometry system (FACS) studies confirmed that the cellular uptake of NDs could be efficiently enhanced by TPGS decoration. The transport mechanism of NDs/CUR and TPGS coated ones was mainly through an energy dependent, clathrin-mediated and caveolin-mediated endocytosis, and the endocytosis of NDs/CUR was also via macropinocytosis. Furthermore, the Papp value (AP-BL) of NDs/CUR and NDs/CUR/TPGS was 2.09- and 3.86- fold higher than that of the CUR suspension. All the results demonstrated that the pharmacological activates and intestinal permeability of CUR across Caco-2 cell monolayer was greatly enhanced by NDs/CUR/TPGS nanocomplexes. Thus NDs could be a promising oral drug delivery platform for improving the intestinal permeability and oral bioavailability of poorly soluble drugs.

Carboxylic acids and their corresponding carboxylate anions are generally utilized as Brønsted acids/bases and oxygen nucleophiles in organic synthesis. However, a few asymmetric reactions have used carboxylic acids as electrophiles. Although chiral thioureas bearing both arylboronic acid and tertiary amine were found to promote the aza-Michael addition of BnONH2 to α,β-unsaturated carboxylic acids with moderate to good enantioselectivities, the reaction mechanism remains to be clarified. Detailed investigation of the reaction using spectroscopic analysis and kinetic studies identified tetrahedral borate complexes, comprising two carboxylate anions, as reaction intermediates. We realized a dramatic improvement in product enantioselectivity with the addition of 1 equiv of benzoic acid. In this aza-Michael reaction, the boronic acid not only activates the carboxylate ligand as a Lewis acid, together with the thiourea NH-protons, but also functions as a Brønsted base through a benzoyloxy anion to activate the nucleophile. Moreover, molecular sieves were found to play an important role in generating the ternary borate complexes, which were crucial for obtaining high enantioselectivity as demonstrated by DFT calculations. We also designed a new thiourea catalyst for the intramolecular oxa-Michael addition to suppress another catalytic pathway via a binary borate complex using steric hindrance between the catalyst and substrate. Finally, to demonstrate the synthetic versatility of both hetero-Michael additions, we used them to accomplish the asymmetric synthesis of key intermediates in pharmaceutically important molecules, including sitagliptin and α-tocopherol.

In a practical feeding trial at Ouwehand Zoo, plasma concentrations of vitamin A1, calcidiol (D3), α-tocopherol (E), and B1 in 17 Humboldt penguins ( Spheniscus humboldti) were measured before and after supplementation to gain insight into the effect of supplementing these vitamins in animals being fed thawed frozen-fish diets. None of the penguins received vitamin supplements for at least 6 mo before the supplementation trial, which was conducted prior to their normal nesting and molting period. During the trial period, eight penguins received daily vitamin A1, D3, tocopheryl acetate, and B1 supplementation placed in their fish immediately prior to feeding and nine control penguins received no supplementation. Concentrations of vitamins A1, D3, α-tocopherol, and B1 were also measured in the thawed ready-to-feed fish. Concentrations of vitamins B1 and α-tocopherol were below the Association of Zoos and Aquariums (AZA) recommendations for penguin diets, while concentrations of vitamins A1 and D3 were far above AZA recommendations. At the start of the study and after 70 days of supplementation, plasma concentrations were determined for these vitamins. Vitamin B1 concentrations in plasma increased significantly ( P < 0.05) between Day 0 (mean 39.9 μg/L) and day 70 (mean 160.5 μg/L) in the supplemented group. Plasma vitamin D3 and α-tocopherol did not show a significant change. Vitamin A1 levels in the supplemented group decreased significantly from 1.65 mg/L on day 0 to 1.4 mg/L on day 70. In the control group no significant changes were observed. The results of the study support the necessity of supplementing vitamin B1 in penguins fed thawed frozen fish. Depletion of vitamin A and E concentrations in frozen food fish over time support recommendations to regularly measure vitamin concentrations in different batches of frozen fish.

The relationship between C-reactive protein (CRP) levels and plasma antioxidants has been established in adults. However, the association has been rarely investigated in healthy children. Thus, we examined the cross-sectional association of high-sensitivity CRP (hs-CRP) levels with fat-soluble plasma antioxidant concentrations in a cohort of healthy prepubertal children. We determined hs-CRP levels in 543 healthy six⁻eight-year-old children using a high-sensitivity CRP enzyme-linked immuno sorbent assay (ELISA) kit. The plasma concentrations of lipids, apolipoproteins and lipid-soluble antioxidants (α-tocopherol, γ-tocopherol, lycopene, α-carotene, β-carotene and retinol) were determined using standardized methods. Pearson correlation analysis showed significant correlations between plasma hs-CRP and α-carotene and retinol concentrations. After adjusting by sex, body mass index (BMI) and lipid levels, only the association with retinol remains significant, with children in the highest hs-CRP tertile group (hs-CRP ≥ 0.60 mg/dL) showing significantly lower levels of retinol than those from the tertiles 1 and 2. A stepwise linear regression selected retinol, BMI, apo A-I and sex as predictors of hs-CRP levels, in a model explaining 19.2% of the variability of hs-CRP. In conclusion, in healthy prepubertal children, after adjusting by sex, BMI and lipid levels, hs-CRP concentrations were highly associated with plasma retinol, which is transported in blood bound to retinol-binding protein but were not associated with the lipoprotein-bound antioxidants.

Breastfeeding is positively associated with several outcomes reflecting early brain development and cognitive functioning. Brain neuroimaging studies have shown that exclusively breastfed children have increased white matter and subcortical gray matter volume compared to formula-fed children. However, it is difficult to disentangle the effects of nutrition in breast milk from other confounding factors that affect brain development, particularly in studies of human subjects. Among the nutrients provided by human breast milk are the carotenoid lutein and the natural form of tocopherol, both of which are selectively deposited in brain. Lutein is the predominant carotenoid in breast milk but not in most infant formulas, whereas infant formulas are supplemented with the synthetic form of tocopherol. In this study, a non-human primate model was used to investigate the effects of breastfeeding versus formula-feeding, as well as lutein and natural RRR-α-tocopherol supplementation of infant formula, on brain maturation under controlled experimental conditions. Infant rhesus macaques (Macaca mulatta) were exclusively breastfed, or were fed infant formulas with different levels and sources of lutein and α-tocopherol. Of note, the breastfed group were mother-reared whereas the formula-fed infants were nursery-reared. Brain structural and diffusion MR images were collected, and brain T2 was measured, at two, four and six months of age. The mother-reared breastfed group was observed to differ from the formula-fed groups by possessing higher diffusion fractional anisotropy (FA) in the corpus callosum, and lower FA in the cerebral cortex at four and six months of age. Cortical regions exhibiting the largest differences include primary motor, premotor, lateral prefrontal, and inferior temporal cortices. No differences were found between the formula groups. Although this study did not identify a nutritional component of breast milk that could be provided to infant formula to facilitate brain maturation consistent with that observed in breastfed animals, our findings indicate that breastfeeding promoted maturation of the corpus callosum and cerebral cortical gray matter in the absence of several confounding factors that affect studies in human infants. However, differences in rearing experience remain as a potential contributor to brain structural differences between breastfed and formula fed infants.

Persistent physical impairment is frequently encountered after critical illness. Recent data point towards mitochondrial dysfunction as an important determinant of this phenomenon. This narrative review provides a comprehensive overview of the present knowledge of mitochondrial function during and after critical illness and the role and potential therapeutic applications of specific micronutrients to restore mitochondrial function. Increased lactate levels and decreased mitochondrial ATP-production are common findings during critical illness and considered to be associated with decreased activity of muscle mitochondrial complexes in the electron transfer system. Adequate nutrient levels are essential for mitochondrial function as several specific micronutrients play crucial roles in energy metabolism and ATP-production. We have addressed the role of B vitamins, ascorbic acid, α-tocopherol, selenium, zinc, coenzyme Q10, caffeine, melatonin, carnitine, nitrate, lipoic acid and taurine in mitochondrial function. B vitamins and lipoic acid are essential in the tricarboxylic acid cycle, while selenium, α-tocopherol, Coenzyme Q10, caffeine, and melatonin are suggested to boost the electron transfer system function. Carnitine is essential for fatty acid beta-oxidation. Selenium is involved in mitochondrial biogenesis. Notwithstanding the documented importance of several nutritional components for optimal mitochondrial function, at present, there are no studies providing directions for optimal requirements during or after critical illness although deficiencies of these specific micronutrients involved in mitochondrial metabolism are common. Considering the interplay between these specific micronutrients, future research should pay more attention to their combined supply to provide guidance for use in clinical practise.

1. A total of 1440 one-day-old Ross 308 male broilers were allocated to twelve dietary treatments to evaluate dose-dependent effects of α-tocopheryl acetate (α-TOA) combined with zinc (Zn) supplementation on humoral and cellular immune responses, antioxidant enzymes, serum and hepatic contents of vitamins and minerals in broilers. 2. Three levels of supplemental α-TOA (0, 150 and 300 mg/kg) and four levels of Zn (0, 100, 200 and 400 mg/kg) were combined as a completely randomised design as a 3×4 factorial arrangement. 3. Concentrations of serum α-tocopherol and selenium were influenced by the interaction of α-TOA and Zn. The interaction of α-TOA and Zn affected malondialdehyde concentration in serum and liver (P<0.05). Incremental amounts of supplemental Zn augmented the effects of α-TOA in reducing serum and hepatic malondialdehyde concentrations. 4. The interaction of α-TOA and Zn on antibody titres (P < 0.05) was such that increasing level of Zn at each α-TOA level led to a linear enhancement in antibody titre. Moreover, dietary supplementation with α-TOA and Zn resulted in an increase in relative weight of lymphoid organs (thymus, bursa, spleen; P<0.05) along with an increase in humoral and cellular immune responses (P<0.05). 5. In conclusion, α-TOA with Zn showed interactive effects in improving oxidative stability and humoral immune responses, which could result from their impact on the concentrations of antioxidant vitamins and minerals in tissues.