Wolman disorder (WD) was first described in Iranian-Jewish (IJ) children, and it is caused by a deficiency of the lysosomal acid lipase (LAL). Newborns with WD are healthy and active at birth but soon develop severe malnutrition symptoms and often die before 1 year. In particular, spleens, livers, bone marrows, intestines, adrenal glands, and lymph nodes accumulate harmful amounts of lipids. G87V mutation in LIPA is responsible for Wolman disorder. Some reports suggest that δ-tocopherol can reduce lipid accumulation in cholesterol storage disorders. Hence, we used δ-tocopherol for the virtual screening process in this study. Initially, the lead compounds were docked with native and G87V mutant LIPA. Subsequently, the ADME and toxicity parameters for screened compounds were determined to ensure the safety profiles. Finally, the molecular dynamics simulations result indicated that dl-alpha-Tocopherol-13C3, a molecule obtained from the PubChem database, is identified as a potential and stable lead molecule that could be effective against the G87V mutant form of LIPA.

The widespread utilization of mupirocin to treat methicillin-resistant Staphylococcus aureus (MRSA)-caused infectious diseases has led to the emergence of mupirocin-resistant Staphylococcus aureus (MuRSA), posing a serious global medical threat. In order to counteract MuRSA, we develop a d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) modified mupirocin and silver complex (TPGS/Mup-Ag) to combat MuRSA. The surfactivity of TPGS endows Mup-Ag with a homogeneous and small particle size (∼16 ​nm), which significantly enhances bacterial internalization. Silver ions are released from the mupirocin-Ag complex (Mup-Ag) to exert a synergistic antibacterial activity with mupirocin. Results manifest that our strategy reduces the concentration of mupirocin that induces 50% bacterial death from about 1000 ​μmol/mL to about 16 ​μmol/mL. In vitro bacterial infection model suggests that TPGS/Mup-Ag can not only eliminate both intracellular and inhibit bacterial adhesion, but also living cells are not affected. Results of in vivo experiments demonstrate that TPGS/Mup-Ag can effectively inhibit the progression of skin infection and accelerate wound healing, as well as alleviate systemic inflammation in both the subcutaneous infection model and the wound infection model. Furthermore, this study may contribute to the development of therapeutic agents for antibiotic-resistant bacteria and offer ideas for silver-based bactericides.

The present investigation was designed to improve drought stress tolerance in eggplant (Solanum melongena L.) through the exogenous application of α-tocopherol (TOC). For exogenous application, two modes, i.e., foliar spray (FS) and pre-sowing seed treatment (PS), were used. Water deficiency treatment (50% field capacity (FC)) was applied on 32-day-old seedlings of two eggplant cultivars, i.e., Janak and Black Beauty. Five levels of TOC (0 mg/L, 50 mg/L PS, 100 mg/L PS, 50 mg/L FS, and 100 mg/L FS) were applied as PS and FS. Pre-sowing seed treatment was conducted before seed sowing, while FS treatment after 30 days of drought stress treatment. After 15 days of TOC as an FS application, it was observed that drought stress significantly reduced plant growth (5-15%) and chlorophyll contents (4-10%), while it increased proline (4-6%), glycine betaine (GB) (5-10%), malondialdehyde (MDA) (10.8%), hydrogen peroxide (15-16%), relative membrane permeability (RMP) (5-8%), and the activities of peroxidase (7-8%) and superoxide dismutase (12-15%) in both eggplant cultivars. The TOC application (FS and PS) exhibited a positive role in overcoming the adverse effect of water stress on eggplants. Plant growth increased (15-18%) as a result of the application of TOC, which could be linked with improved chlorophyll, ascorbic acid (AsA), GB, proline, total soluble proteins (TSP), and the activities of peroxidase (POD) and superoxide dismutase (SOD) activities. The reactive oxygen species H2O2 was also decreased by TOC application. Overall, TOC as a foliar spray was more effective in improving the accumulation of proline, GB, AsA, and activities of SOD and POD enzymes, while PS treatment was more effective in reducing RMP and improving the TSP of eggplant. Cv. Black Beauty was comparatively better in root dry weight, chlorophyll a and b, and MDA contents, while cv. Janak in RMP, AsA, TSP, and activity of the POD enzyme. It can be inferred that the application of TOC was useful in counteracting the harmful effects of drought stress on both cultivars of eggplants.

The development of new vaccine adjuvants represents a key approach to improvingi the immune responses to recombinant vaccine antigens. Emulsion adjuvants, such as AS03 and MF59, in combination with influenza vaccines, have allowed antigen dose sparing, greater breadth of responses and fewer immunizations. It has been demonstrated previously that emulsion adjuvants can be prepared using a simple, low-shear process of self-emulsification (SE). The role of alpha tocopherol as an immune potentiator in emulsion adjuvants is clear from the success of AS03 in pandemic responses, both to influenza and COVID-19. Although it was a significant formulation challenge to include alpha tocopherol in an emulsion prepared by a low-shear process, the resultant self-emulsifying adjuvant system (SE-AS) showed a comparable effect to the established AS03 when used with a quadrivalent influenza vaccine (QIV). In this paper, we first optimized the SE-AS with alpha tocopherol to create SE-AS44, which allowed the emulsion to be sterile-filtered. Then, we compared the in vitro cell activation cytokine profile of SE-AS44 with the self-emulsifying adjuvant 160 (SEA160), a squalene-only adjuvant. In addition, we evaluated SE-AS44 and SEA160 competitively, in combination with a recombinant cytomegalovirus (CMV) pentamer antigen mouse.

Our previous work showed that citrinin (CTN) produced bay Penicillium citrinum inhibited the production of aflatoxin by Aspergillus parasiticus. We also reported that CTN was non-enzymatically converted to a novel CTN-KA adduct with kojic acid (KA) in aqueous condition. We herein observed that unlike CTN, the CTN-KA adduct does not show antimicrobial activity against Escherichia coli or Bacillus subtilis or any cytotoxic effect on HeLa cells, suggesting that CTN was detoxified by KA by the formation of the CTN-KA adduct. To examine the function of KA production by fungi, we isolated A. parasiticus mutants with impaired KA production. When the mutants were incubated in either liquid or agar medium supplemented with CTN, they were more susceptible to CTN than the wild KA-producing strain. The same results were obtained when we used the A. oryzae KA-producing strain RIB40 and KA-non-producing strains. When KA was added to the CTN-containing agar medium, the inhibition of growth by CTN was remarkably mitigated, suggesting that the production of KA protected the fungal growth from CTN's toxicity. We also observed that CTN enhanced the production of KA by A. parasiticus as well as A. oryzae strains. Reverse transcription-PCR showed that CTN enhanced the expression of KA biosynthetic genes (kojA, kojR, and kojT) of A. parasiticus. However, the enhancement of KA production with CTN was repressed by the addition of α-tocopherol or butylated hydroxy anisole, suggesting that KA production is enhanced by oxidative stress via the formation of reactive oxygen species caused by CTN. In contrast, α-tocopherol did not affect inhibition of AF production as well as fungal growth by CTN, suggesting that the regulation of these inhibitions with CTN might be different from that of KA production. We propose a regulation scheme of CTN for each of KA production, AF production, and fungal growth in A. parasiticus.

Tocopherols are natural bioactive compounds with several health benefits. This study evaluated the effect of different ratios of α- and δ- tocopherol homologs to protect sunflower oil (SO) and olive pomace oil (OPO) against oxidation. A synergistic effect was recorded when the two tocopherols were combined at a ratio of 7:1 (α-T/δ-T). The oil samples were exposed to accelerated oxidation conditions using a Rancimat (90 °C and airflow of 15 L/h for 24 h) and protection from tocopherols was compared with that from butylated hydroxytoluene (BHT). Assessment of oil stability was examined using well-known parameters such as peroxide value (PV), thiobarbituric acid reactive substances (TBARS), p-anisidine value (p-AV), conjugated dienes (CD) and trienes (CT), and total oxidation (Totox) value, which were all significantly reduced when tocopherols were added at a ratio of 7:1 α-T/δ-T. Primary oxidative compounds measured according to PV were only reduced in SO samples (6.11%). Off-flavor compounds measured via TBARS assay in SO samples were reduced by above 20%, while p-AV was also reduced. CDvalue was correlated with PV in SO samples, while the 7:1 mixture was more effective than BHT for CTvalue. Total oxidation values in SO samples and OPO samples were reduced by 6.02% and 12.62%, respectively. These values in SO samples also provided a remarkable correlation (R2 > 0.95) with incubation time. Moreover, the synergistic effect was not only effective in reducing the oxidation values of oil samples, but also in lowering the degradation rate of tocopherols. Protective effects from tocopherols were mainly observed in SO samples, as OPO samples were more resistant to oxidation processes. This effect was even observed in fatty acid analysis, where the 7:1 mixture provided better results than BHT-spiked samples. Thus, it is suggested that tocopherol mixtures might be used as a natural preservative in the food industry to restrain lipid oxidation processes.

Red-flowered oil-tea camellia (ROC) is an important woody oil species growing in the south, and its oil has high nutritional value. There are four main species of ROC in China, namely, Camellia chekiangoleosa (CCH), Camellia polyodonta (CPO), Camellia semiserrata (CSE) and Camellia reticulata (CRE). Reports on the comprehensive comparative analysis of ROC are limited. This study investigated the fruit characteristics and nutritional components of four ROC fruits, and the results showed that ROC had high oil content with levels of 39.13%-58.84%, especially the CCH fruit, which reached 53.6-58.84%. The contents of lipid concomitants of ROC oil were also substantial, including β-amyrin (0.87 mg/g-1.41 mg/g), squalene (0.43 mg/g-0.69 mg/g), β-sitosterin (0.47 mg/g-0.63 mg/g) and α-tocopherol (177.52 μg/g-352.27 μg/g). Moreover, the transverse diameter(TD)/longitudinal diameter (LD) of fruits showed a significant positive correlation with the oil content, and ROC fruits with thinner peels seemed to have better oil quality, which is similar to the result of the oil quality evaluation obtained by the gray correlation coefficient evaluation method. Four ROC oils were evaluated using the gray correlation coefficient method based on 11 indicators related to the nutritional value of ROC. CCH oil had the highest score of 0.8365, and YS-2 (a clone of CCH) was further evaluated as the best CCH oil. Finally, the results of heatmap analysis showed that triglycerides could be used as a characteristic substance to distinguish CCH oil from the other three ROC oils. The PLSDA (Partial least squares regression analysis) model and VIP (Variable important in projection) values further showed that P/S/O, P/O/O, P/L/L, P/L/Ln, S/S/O, S/O/O and P/S/S (these all represent abbreviations for fatty acids) could be used as characteristic differential triglycerides among the four ROC oils. This study provides a convenient way for planters to assess the nutritional quality of seed oil depending on fruit morphology and a potential way to distinguish between various ROC oils.

Although observational studies have suggested associations between circulating antioxidants and many mental disorders, causal inferences have not been confirmed. Mendelian randomization (MR) analyses were conducted using summary-level statistics from genome-wide association studies (GWASs) to explore whether genetically determined absolute circulating antioxidants (i.e., ascorbate, retinol, β-carotene, and lycopene) and metabolites (i.e., α- and γ-tocopherol, ascorbate, and retinol) were causally associated with the risk of six major mental disorders, including anxiety disorders (AD), major depressive disorder (MDD), bipolar disorder (BIP), schizophrenia (SCZ), post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). MR analyses were performed per specific-outcome databases, including the largest GWAS published to date (from 9725 for OCD to 413,466 for BIP participants), UK Biobank (over 370,000 participants), and FinnGen (over 270,000 participants), followed by meta-analyses. We found no significant evidence that genetically determined diet-derived circulating antioxidants were significantly causally associated with the risk of the six above-mentioned major mental disorders. For absolute antioxidant levels, the odds ratios (ORs) ranged from 0.91 (95% CI, 0.67-1.23) for the effect of β-carotene on OCD to 1.18 (95% CI, 0.90-1.54) for the effect of ascorbate on OCD. Similarly, for antioxidant metabolites, ORs ranged from 0.87 (95% CI, 0.55-1.38) for the effect of ascorbate on MDD to 1.08 (95% CI, 0.88-1.33) for the effect of ascorbate on OCD. Our study does not support significant causal associations of genetically determined diet-derived circulating antioxidants with the risk of major mental disorders.

In this study, an alternative debittering technique for olives, invented and patented by Prof. Vassilis Dourtoglou, was employed. Olive fruits (Olea europaea cv. Megaritiki) were stored under CO2 atmosphere immediately after harvest for a period of 15 days. After the treatment, a sensory evaluation between the olives stored under CO2 and those stored under regular atmospheric conditions (control) was performed. Additionally, the CO2-treated olives were used for the cold press of olive oil production. The volatile profile of the olive oil produced was analyzed using headspace solid-phase microextraction (HS-SPME) and gas chromatography coupled to mass spectrometry (GC-MS). A total of thirty different volatile compounds were detected. The volatile characteristics of olive oil are attributed, among others, to aldehydes, alcohols, esters, hydrocarbons, alkanes, and terpenes. The volatile compounds' analysis showed many differences between the two treatments. In order to compare the volatile profile, commercial olive oil was also used (produced from olives from the same olive grove with a conventional process in an industrial olive mill). The antioxidant activity, the content of bioactive compounds (polyphenols, α-tocopherol, carotenoids, and chlorophylls), and the fatty acids' profile were also determined. The results showed that the oil produced from CO2-treated olives contains different volatile components, which bestow a unique flavor and aroma to the oil. Moreover, this oil was found comparable to extra virgin olive oil, according to its physicochemical characteristics. Finally, the enhanced content in antioxidant compounds (i.e., polyphenols) not only rendered the oil more stable against oxidation but also better for human health. The overall quality of the olive oil was enhanced and, as such, this procedure holds great promise for future developments.

Fluconazole (FLZ) is the most widely used antifungal agent for treating cutaneous candidiasis. Although oral FLZ has been proved to be effective, the incidence of side effects necessitates the development of an effective formulation that could surpass the pitfalls associated with systemic availability. Accordingly, this research aimed at developing a self-assembled mixed micelles topical delivery system to enhance the topical delivery of the drug. Self-assembled mixed micelles were developed using D-α-tocopheryl polyethylene glycol 1000 succinate and phospholipids and optimized using Box-Behnken design. The optimized formulation with minimized size was then tested in vivo for the antifungal activity against C. albicans in immunocompromised mice. Treatment with the optimized formulation led to decreased peripheral erythema as well as lesions due to fungal infection in comparison to raw FLZ loaded gel. Therefore, the developed formulation was found to be a promising vehicle for the treatment of cutaneous candidiasis.

Arbuscular mycorrhizal fungi may alleviate water stress in plants. Although several protection mechanisms have already been described, little information is available on how these fungi influence the hormonal response to water stress at an organ-specific level. In this study, we evaluated the physiological and hormonal responses to water stress in above and below-ground tissues of the legume grass Trifolium repens colonized by the arbuscular mycorrhizal fungus Rhizoglomus irregulare. Plants were subjected to progressive water stress and recovery. Different leaf and root physiological parameters, as well as phytohormone levels, were quantified. Water-stressed mycorrhizal plants showed an improved water status and no photoinhibition compared to uncolonized individuals, while some stress markers like α-tocopherol and malondialdehyde content, an indicator of the extent of lipid peroxidation, transiently increased in roots, but not in leaves. Water stress protection exerted by mycorrhiza appeared to be related to a differential root-to-shoot redox signaling, probably mediated by jasmonates, and mycorrhization enhanced the production of the cytokinin trans-zeatin in both roots and leaves. Overall, our results suggest that mycorrhization affects physiological, redox and hormonal responses to water stress at an organ-specific level, which may eventually modulate the final protection of the host from water stress. This article is protected by copyright. All rights reserved.

The lack of vitamins D, B group, calcium and magnesium is common for the diet of the Russian population. It has been previously demonstrated that that the elimination of B vitamin deficiency is a necessary condition for the implementation of vitamin D biological functions. The aim of the research was to assess the effect of a combined deficiency of vitamins D and B group, calcium and magnesium in the diet of rats on biomarkers of micronutrient sufficiency and plasma biochemical indicators. Material amd methods. Male Wistar rats with an initial body weight of 66±1 g were randomly assigned to one of five groups. The rats of the 1st group (Control) were fed a standard semi-synthetic diet (SD) for 28 days. The combined deficit of vitamins D and B group, calcium and magnesium in rats of four experimental groups was caused by a 5-fold decrease in their content in the vitamin mixture and 2-fold decrease in their content in mineral mixture of the SD for 23 days. Over the next 5 days, the rats of 2nd group (+В+D+Ca+Mg) were fed a diet replenished for all missing vitamins and minerals, the rats of 3rd group (-В+D+Ca+Mg) were fed a diet with continued deficiency of B group vitamins, the rats of the 4th group (+В+D-Ca-Mg) were fed a diet with continued lack of calcium and magnesium, the diet of the 5th group (-B-D-Ca-Mg) was not replenished. Vitamins B1 and B2 in lyophilized liver and brain and urine, riboflavin in plasma and 4-pyridoxic acid in urine were determined by fluorimetric methods, 25(OH)D in plasma was determined by ELISA, the level of vitamins A and E in blood plasma and lyophilized liver, of vitamin E in whole brain - by HPLC. Biochemical parameters of blood plasma were determined using a biochemical analyzer. Results. In rats of the 5th group (-B-D-Ca-Mg), there were 3.4-fold increase (p<0.05) in iron plasma level, 1.7-fold elevation (p<0.10) in alkaline phosphatase activity, and 1.8-fold decrease (p<0.05) in alanine aminotransferase (ALT) activity on the background of the increase in α-tocopherol blood plasma level by 26.7% (p<0.05) and liver content by 2.0 fold (p<0.05) relative to the indicators in animals who hadn't passed the deficiency of micronutrients (Control) and / or from the 2nd group (+B+D+Ca+Mg). The lack of B group vitamins in the diet, which persisted during the correction of vitamin D, calcium and magnesium deficiency in rats of the 3rd group (-B+D+Ca+Mg), inhibited the recovery of diagnostically significant biochemical parameters of blood plasma (namely, an increased level of glucose, iron, triglycerides, cholesterol, α-tocopherol, increased alkaline phosphatase activity and reduced ALT activity) to the level in animals of the control group and/or rats fed the diet replenished for all missing micronutrients (+B+D+Ca+Mg). Conclusion. Combined deficiency of several micronutrients led to changes in biochemical blood parameters. Reduced intake of calcium and magnesium during the correction of the lack of vitamins D and B group in the diet can have a negative impact on vitamin B2 status. Even under normal dietary vitamin E intake the combined deficiency of several other micronutrients affected the metabolism of this vitamin (increased levels of vitamin E in the liver and blood plasma of animals). Chronic combined alimentary deficit of B vitamins, calcium and magnesium, which is characteristic in the diet of the Russian population, reduces vitamin D bioavailability, which justifies the expediency of using vitamin-mineral complexes.

Coccidiosis is a worldwide epidemic intestinal disease with high incidence, which causes huge economic losses. Halofuginone hydrobromide (HF) is widely applied as an effective anticoccidial drug in the poultry industry. However, its therapeutic efficacy is severely restrained due to toxic effects, poor aqueous solubility and low permeability. Nanotechnology can improve the biological effect of drugs, and thus, reduce administered doses and toxic effects. The objective of this study was to investigate the therapeutic and preventive potential of novel HF-loaded D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) polymer micelles (HTPM) for preventing coccidiosis in chickens. The HTPM were approximately spherical with a hydrodynamic diameter of 12.65 ± 0.089 nm, a zeta potential of 8.03 ± 0.242 mV, a drug loading of 14.04 ± 0.12%, and an encapsulation efficiency of 71.1 ± 4.15%. HF was encapsulated in the polymer micelles through interactions with TPGS, as characterized by X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy. Cellular take up assays showed that TPGS polymer micelles could enhance drug internalization to alleviate intestinal apoptosis induced by coccidiosis and promote the necrosis of second-generation merozoites of E. tenella. Notably, clinical trials proved that 1.5 mg L-1 HTPM had a stronger anticoccidial effect on E. tenella than that of 3 mg kg-1 HF premix. Amplicon sequencing identified that HTPM could alleviate coccidiosis by restoring the structure of the gut microbiome. These findings indicated that the anticoccidial efficacy of HF was significantly enhanced after being encapsulated in polymer micelles, and further demonstrated the potential protective application of nano-encapsulating anticoccidial drugs as a promising approach to control coccidiosis in poultry. In summary, HTPM hold huge potential as an effective therapeutic agent for coccidiosis.

In recent years, there has been a great interest in the potential use of contact lenses as eye drug delivery systems. Static (individual layers of the cornea, sclera and retina) as well as dynamic barriers (blood flow) pose a serious challenge to the effective delivery of the drug substance to the eyeball. The current ophthalmic systems are not optimal for patients, especially in the form of eye drops, where almost 95% of the drug contained in them is lost through the process of absorption through the conjunctiva or tear drainage. This article describes in vitro experiments that examined the use of contact lenses in the context of drug treatment in infectious, inflammatory, allergic, and glaucomatous diseases. Various techniques used to modify the materials as well as their impact on drug release kinetics were discussed. It has also been demonstrated that these methods can be used in practice during in vivo research, both in animal models as well as in sick and healthy people. The advantages of using controlled-release drug systems in the form of contact lenses are the drug dosing regimen, bioavailability and the prolonged residence time of drugs in the eyeball.

Inflammation has been implicated in cardiovascular disease and tocotrienols are potent hypocholesterolemic agents that reduce β-hydroxy-β-methyl-glutaryl coenzyme A reductase activity, which is degraded via the ubiquitin-proteasome pathway. Impact of various tocotrienols (α-, γ-, or δ-tocotrienol) treatments inhibit the chymotrypsin-like activity of 20S rabbit muscle proteasome (>50%) in RAW 264.7 cells and BALB/c mice. Moreover, the effect of various tocotrienols (α-, γ-, or δ-tocotrienol), α-tocopherol, quercetin, riboflavin, (-) Corey lactone, amiloride, dexamethasone supplemented diets fed to chickens (4-weeks) resulted in reduction of total cholesterol, LDL-cholesterol, and triglycerides. This trend was also observed in macrophages from RAW 264.7 cells, in LPS-induced thioglycolate-elicited peritoneal macrophages derived from C57BL/6, BALB/c, LMP7/MECL-1-/-, and PPAR-α-/- knockout mice from young (4-week-old) and senescent (42-week-old) mice, resulting in significant inhibition of TNF-α and nitric oxide levels (30% to 70%), blocked degradation of P-IκB protein, and decreased activation of NF-κB, followed gene suppression of mRNA levels of TNF-α, IL-1β, IL-6, and iNOS. In human study, normal or hypercholesterolemic subjects administered two capsules/d of NS-7 or NS-6 (4-weeks) showed decrease in serum CRP, NO, γ-GT, total cholesterol, LDL-cholesterol, and triglycerides levels in normal as compared to hypercholesterolemic subjects (12% to 39%). In second study, hypercholesterolemic subjects were given increasing doses of δ-tocotrienol (125 mg, 250 mg, 500 mg, and 750 mg/day) plus AHA Step-1 diet (4-weeks). The most effective dose of tocotrienols (250 mg/day) may be used to lower serum NO (40%), CRP (40%), MDA (34%), γ-GT (22 %), and inflammatory cytokines IL-1α, IL-12, IFN-γ by 15% to 17%, and increase TAS levels by 22%.

This article reviews what is presently known about the biological roles of the diet-derived compound ergothioneine (ET). ET seems important to humans because it is rapidly taken up from the diet by a transporter largely or completely specific for ET, and once taken up it is retained within the body for weeks or months. The various possible functions of ET in vivo are explored. Much emphasis has been placed on the antioxidant properties of ET, but although these are well established in vitro, the evidence that antioxidant activity is the principal function of ET in vivo is weak. ET is not unique in this: The evidence for the antioxidant roles of vitamin C and polyphenols such as the flavonoids in vivo is also weak. By contrast, α-tocopherol has demonstrated in vivo antioxidant effects in humans. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 14 is March 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

We hypothesized that tocopherol succinate (TOS) and D-α-tocopherol polyethylene2000 succinate (TPGS2000) micelles could work as a drug delivery system while enhancing the anti-cancer efficacy of doxorubicin lauryl hydrazone derivative (DOXC12) for the treatment of glioblastoma. The DOXC12-TOS-TPGS2000 micelles were formulated with synthesized DOXC12 and TPGS2000. They showed a high drug loading of hydrophobic DOXC12 (29%), a size of <100 nm and a pH sensitive drug release behaviour. In vitro, fast uptake of DOXC12-TOS-TPGS2000 micelles by GL261 cells was observed. For cytotoxicity, DOXC12-TOS-TPGS2000 micelles were evaluated on two glioblastoma cell lines and showed synergism between DOXC12 and TOS-TPGS2000. The higher cytotoxicity of DOXC12-TOS-TPGS2000 micelles was mainly caused by necrosis. The DOXC12-TOS-TPGS2000 micelles seem to be a promising delivery system for enhancing the anticancer efficacy of doxorubicin in glioblastoma (GBM).

Vit E is known as one of the most important antioxidant. It has been previously approved that cereal grains and leafy plants are considered as the main source for α-tocopherol (Vit E). One of the recommended therapies for male infertility would be the Vit E therapy. Following Vit E consumption the semen parameters such as sperm concentration, ejaculation volume, sperm progressive motility, and in vitro function (zone binding assay) have been significantly improved. Therefore, present study was designed to investigate the effects of oral administration of cereal grain and seeds on reproductive performance of local cocks. During a period of 63 weeks, 100 local (Iraqi breed) rooster chicks were randomly divided into the five groups (n=20). Animals in group 1 served as control group and had not received any supplementations in their diet. The animals in the Groups 2-5 received diets which were fortified with 100, 200, 300, and 400 g of cereal grain and legume seeds pure germs. The results of the current study showed that the total number of spermatozoa and percentages of abnormal sperm were decreased by adding more amount of germ of cereal grain and seeds (P<0.01). Increased germ of cereal grain and seeds was not associated with pH volume, colour, consistency and motility of the sperm compared to corresponding rates in control group. Phospholipids content and thiobarbituric acid reactive substance of semen sample as well as density of ejaculate (sperm/µl) were decreased by adding increasing germ of cereal grain and seeds in diet of rosters. Weight of testis decreased by increasing levels of cereal grains and legume seeds germ in the diets (P<0.05).

It is well documented that choline is known as one of the essential ingredients of phospholipids. Choline acts as a determinative element for appropriate cell membrane functions. On the other hand α-tocopherol (Vit E) is a fat-soluble vitamin. This vitamin acts as a strong antioxidant in the living body's defense system against oxidative stress. Lipid peroxidation in peripartum and early lactating cows is significantly increased while the level of serum Vit E is decreases dramatically. These concomitant physiological changes demonstrate a higher level of oxidative stress subsequently leads to serious health issues in dairy cows. Therefore, the present research was designed to investigate the following items in dairy cattle: 1) evaluation of the possible changes in serum protein fractions, and 2) comparing the oxidative status of orally RPC and vitamin E supplementation in dairy cows in early lactation period. In the current study 30 early lactating primiparous and multiparous Holstein cows (body condition score (BCS)=2.51 ± 0.10) were used beginning five weeks postpartum. All the animals were randomly divided in to three groups (n=10) (number of lactation=2.61). The animals were randomly assigned to receive one of the following treatments. Group 1 served as control group were not received any supplement. The second group was supplemented with 90 g/d of RPC (Reashre Choline, Balchem, USA). The third group was administrated 4400 IU/d vitamin E (Roche, Vitamins Ltd; Switzerland). In the current study, serum protein electrophoresis showed four main fractions as follows: albumin, α-globulin, β-globulin, and γ-globulin. The recorded data showed that the percentages of albumin and γ-globulin fractions were higher in treated groups compared to the control group. In the animals supplementing with RPC and vitamin E the percentages of serum albumin increased to the value of 37. 70±1.63 and 38.21±1.28 respectively compare to the control group (34.69±1.21), which were significant (P<0.05).

Bee-honey solution (BHS) is considered a plant growth multi-biostimulator because it is rich in osmoprotectants, antioxidants, vitamins, and mineral nutrients that can promote drought stress (DtS) resistance in common bean plants. As a novel strategy, BHS has been used in a few studies, which shows that the application of BHS can overcome the stress effects on plant productivity and can contribute significantly to bridging the gap between agricultural production and the steady increase in population under climate changes. Under sufficient watering (SW (100% of crop evapotranspiration; ETc) and DtS (60% of ETc)), the enhancing impacts of foliar application with BHS (0%, 0.5%, 1.0%, and 1.5%) on growth, productivity, yield quality, physiological-biochemical indices, antioxidative defense ingredients, and nutrient status were examined in common bean plants (cultivar Bronco). DtS considerably decreased growth and yield traits, green pod quality, and water use efficiency (WUE); however, application of BHS at all concentrations significantly increased all of these parameters under normal or DtS conditions. Membrane stability index, relative water content, nutrient contents, SPAD (chlorophyll content), and PSII efficiency (Fv/Fm, photochemical activity, and performance index) were markedly reduced under DtS; however, they increased significantly under normal or DtS conditions by foliar spraying of BHS at all concentrations. The negative impacts of DtS were due to increased oxidants [hydrogen peroxide (H2O2) and superoxide (O2•-)], electrolyte leakage (EL), and malondialdehyde (MDA). As a result, the activity of the antioxidant system (ascorbate peroxidase, glutathione reductase, catalase, superoxide dismutase, α-tocopherol, glutathione, and ascorbate) and levels of osmoprotectants (soluble protein, soluble sugars, glycine betaine, and proline) were increased. However, all BHS concentrations further increased osmoprotectant and antioxidant capacity, along with decreased MDA and EL under DtS. What is interesting in this study was that a BHS concentration of 1.0% gave the best results under SW, while a BHS concentration of 1.5% gave the best results under DtS. Therefore, a BHS concentration of 1.5% could be a viable strategy to mitigate the DtS impairment in common beans to achieve satisfactory growth, productivity, and green pod quality under DtS.

Atopic dermatitis is a T-cell mediated inflammatory skin disease with detected elevated levels of histamine in skin or plasma. In this study, the effects of histamine in a TH2 cytokine environment on human keratinocytes and three-dimensional skin models were investigated. These models were used to explore the anti-inflammatory properties of the α-tocopherol-derived long-chain metabolite α-13'-carboxychromanol (α-13'-COOH). Histamine and TH2 cytokine-induced proliferation of keratinocytes was studied using a scratch assay. The inflammatory marker interleukin-8 was significantly increased in healthy and TH2 cytokine-stimulated keratinocytes and skin models after histamine treatment. The incubation of full-thickness skin models with TH2 cytokines and histamine resulted in morphological changes in the epidermal layer, interpreted as hyperkeratosis. α-13'-COOH significantly decreased interleukin-8 in these disease-associated skin models. Histological staining of filaggrin showed skin-strengthening effects following α-13'-COOH treatment, without changes in mRNA expression. Cytokeratin 10 mRNA expression tended to be increased in response to α-13'-COOH. Anti-allergic properties of α-13'-COOH were studied by pre-incubation of human leukocytes with α-13'-COOH. This resulted in reduced sulfido-leukotriene synthesis. The hyperproliferation effect of histamine in atopic dermatitis skin models may be of further interest to the study of disease-associated morphological changes. Moreover, α-13'-COOH is a promising natural compound for the treatment of inflammatory skin diseases.

Since brown rice extract is a rich source of biologically active compounds, the present study is aimed to quantify the major compounds in brown rice and to compare their cytoprotective potential against oxidative stress. The content of the main hydrophobic compounds in brown rice followed the order of cycloartenyl ferulate (CAF) (89.00 ± 8.07 nmol/g) >> α-tocopherol (αT) (19.73 ± 2.28 nmol/g) > γ-tocotrienol (γT3) (18.24 ± 1.41 nmol/g) > α-tocotrienol (αT3) (16.02 ± 1.29 nmol/g) > γ-tocopherol (γT) (3.81 ± 0.40 nmol/g). However, the percent contribution of CAF to the radical scavenging activity of one gram of whole brown rice was similar to those of αT, αT3, and γT3 because of its weaker antioxidant activity. The CAF pretreatment displayed a significant cytoprotective effect on the hydrogen peroxide-induced cytotoxicity from 10 µM, which is lower than the minimal concentrations of αT and γT required for a significant protection. CAF also enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation coincided with the enhancement of the heme oxygenase-1 (HO-1) mRNA level. An HO-1 inhibitor, tin protoporphyrin IX (SnPP), significantly impaired the cytoprotection of CAF. The cytoprotective potential of CAF is attributable to its cycloartenyl moiety besides the ferulyl moiety. These results suggested that CAF is the predominant cytoprotector in brown rice against hydrogen peroxide-induced cytotoxicity.

MicroRNAs (miRNAs) play a key role in the regulation of genes for normal metabolism in the liver. Dysregulation of miRNAs is involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). We aimed to explore changes in circulating miRNA expression in response to delta-tocotrienol (δT3) and alpha-tocopherol (αTF) supplementation and correlate them with relevant biochemical markers in patients with NAFLD. In total, 100 patients with NAFLD were randomized to either receive δT3 (n = 50) 300 mg or αTF (n = 50) 268 mg twice/day for 48 weeks. Plasma expression of miRNA-122, -21, -103a-2, -421, -375 and -34a were determined at baseline, 24 and 48 weeks of intervention using RT-qPCR. Both δT3 and αTF significantly downregulated expression of miRNA-122, -21, -103a-2, -421, -375 and -34a. Moreover, δT3 was more effective than αTF in reducing expression of miRNA-375 and -34a. A significant correlation was observed between miRNA expression and biochemical markers of hepatic steatosis, insulin resistance (IR), oxidative stress (OS), inflammation and apoptosis. δT3 and αTF exert hepato-protective effects by downregulating miRNAs involved in hepatic steatosis, IR, OS, inflammation and apoptosis in patients with NAFLD. Furthermore, δT3 has more pronounced effects than αTF in reducing miR-375 and miR-34a, which are linked to regulation of inflammation and apoptosis.

Exploring and deciphering the biodiversity of oil bodies (OBs) recovered from oilseeds are of growing interest in the preparation of sustainable, natural and healthy plant-based food products. This study focused on chia (Salvia hispanica L.) and camelina (Camelina sativa L.) seed OBs. A green refinery process including ultrasound to remove mucilage, aqueous extraction by grinding and centrifugation to recover OBs from the seeds was used. The microstructure, composition and physical stability of the OBs were examined. Confocal laser scanning microscopy images showed that chia and camelina seed OBs are spherical assemblies coated by a layer of phospholipids and proteins, which have been identified by gel electrophoresis. The mean diameters determined by laser light scattering measurements were 2.3 and 1.6 µm for chia and camelina seed OBs, respectively. The chia and camelina seed OBs were rich in lipids and other bioactive components with, respectively, 64% and 30% α-linolenic acid representing 70% and 53% of the total fatty acids in the sn-2 position of the triacylglycerols, 0.23% and 0.26% phospholipids, 3069 and 2674 mg/kg oil of β-sitosterol, and lipophilic antioxidants: 400 and 670 mg/kg oil of γ-tocopherol. Phenolic compounds were recovered from the aqueous extracts, such as rutin from camelina and caffeic acid from chia. Zeta-potential measurements showed changes from about -40 mV (pH 9) to values that were positive below the isoelectric points of pH 5.1 and 3.6 for chia and camelina seed OBs, respectively. Below pH 6.5, physical instability of the natural oil-in-water emulsions with aggregation and phase separation was found. This study will contribute to the development of innovative and sustainable food products based on natural oil-in-water emulsions containing chia and camelina seed OBs for their nutritional and health benefits.

This study aims to compare the suitability of three extraction techniques (cold pressing, Soxhlet and supercritical fluid extraction (SFE)) to isolate oil from cherry seeds. Oils were examined in terms of extraction yield, fatty acids profile, tocopherols yield and antioxidant activity. Additionally, influence of SFE parameters was evaluated using one-factor-at-a-time design with pressure (200-350 bar), temperature (40-70 °C), flow rate (0.2-0.4 kg/h) and particle size (<800 µm and >800 µm). Oil yields ranged from 2.50% to 13.02%, whereas the highest yield was achieved with SFE. Samples were rich in polyunsaturated fatty acids, regardless of the applied extraction technique. The main fatty acids were linoleic (46.32-47.29%), oleic (40.89-41.65%), palmitic (6.56-8.00%) and stearic (2.21-2.30%) acid. Total tocopherols yield was between 16.63 mg/100 g oil and 60.61 mg/100 g oil, and highest yield was achieved with SFE. Among the tocopherols, γ-tocopherol was the most abundant, followed by α-, δ- and β-tocopherol. Antioxidant activity was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic) cation (ABTS) assays, and the results indicated that SFE extracts exhibited better or comparable antioxidant potential compared to traditional techniques. The comparison between modern and conventional extractions for oil recovery demonstrates pros and cons for the possibility of industrial application.

The content, composition and variation of vitamin compounds in goat milk have been little studied. An experimental design was based on 28 commercial farms, selected considering the main feeding system (based on main forage and especially pasture access), goat breed (Alpine vs Saanen) and reproductive management (seasonal reproduction), in the main French goat milk production area. Each farm received two visits (spring and autumn) that included a survey on milk production conditions and bulk milk sampling. Milk vitamins (A, E, B2, B6, B9, B12) and carotenoid concentrations plus colour indices were evaluated. A stepwise approach determined the variables of milk production conditions that significantly altered milk indicators. The main forage in the diet was the major factor altering goat milk vitamin and carotenoid concentrations and colour indices. Bulk milk from goats eating fresh grass as forage was richer in α-tocopherol (+64%), pyridoxal (+35%) and total vitamin B6 (+31%), and b* index (characterising milk yellowness in the CIELAB colour space) was also higher (+12%) than in milk from goats eating conserved forages. In milk from goats eating fresh grass, concentrations of pyridoxamine, lutein and total carotenoids were higher than in milk of goats fed corn silage (+24, +118 and +101%, respectively), and retinol and α-tocopherol concentrations were higher than in milk of goats fed partially dehydrated grass (+45 and +55%). Vitamin B2 concentration was higher in milk of goats eating fresh grass than in milk of goats fed hay or corn silage as forage (+10%). However, bulk milk when goats had access to fresh grass was significantly poorer in vitamin B12 than when fed corn silage (-46%) and in γ-tocopherol (-31%) than when fed conserved forage. Alpine goats produced milk with higher vitamin B2 and folate concentrations than Saanen goats (+18 and +14%, respectively). Additionally, the milk colour index that discriminates milks based on their yellow pigment contents was 7% higher in milk from Alpine than Saanen herds, but milk from Saanen goats was richer in lutein (+46%). Goat milks were richer in vitamins B2 and B12 and folates, but poorer in vitamin B6 in autumn than in spring (+12, +133, +15 and -13%, respectively). This work highlights that goat milk vitamin and carotenoid concentrations and colour indices vary mainly according to the main forage of the diet and secondly according to the breed and season.

Pili (Canarium ovatum Engl.), an indigenous tree found in the Philippines, is highly regarded for its fruit due to its high economic value. During processing, the pulp is often discarded as waste but contains considerable amounts of oil and bioactive minor lipid components. The present study explored the antioxidant and antibacterial properties of saponified diethyl ether extract of pili pulp oil and related this activity to the nature of compounds present in the extract through GCMS. The extract indicated the elution of 18 major compounds which are mostly cyclic triterpenic (α-and β-amyrin, lupenone, and β-amyrone) and phytosterol (β-sitosterol, brassicasterol, and stigmasterol) class of compounds. Characterization of the bioactivity of the extract showed high antioxidant activities measured by DPPH radical scavenging (EC50: 74.45 ± 1.29 μg/mL) and lipid peroxidation inhibition (EC50: 3.02 ± 0.06 μg/mL) activities that were comparable with that of α-tocopherol. Moreover, an observed bactericidal activity was demonstrated by the extract against E. coli and S. typhi with MIC values of 40 and 35 μg/mL, respectively. The observed bioactivity of the pili pulp oil extract can be attributed to these compounds which may provide desirable health benefits.