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Introduction: Oxidative stress (OS) has been linked to neurodegenerative diseases in numerous epidemiological studies; however, whether it is a pathogenesis or a downstream factor remains controversial. Methods: A two-sample bidirectional Mendelian randomization (MR) analysis was implemented to examine evidence of causality of 15 OS injury markers with 3 major neurodegenerative diseases using available genome-wide association studies statistics. As a main approach, inverse-variance weighted (IVW) analysis was performed. The weighted-median (WM) analysis was used to validate the relationship. In order to investigate the existence of horizontal pleiotropy and correct the IVW estimate, the Radial MR approach was applied. To gauge the consistency and robustness of the findings, several sensitivity and pleiotropy analyses were used. For this analysis, p < 0.05 indicates a nominally causal association; according to the Bonferroni correction test, p < 0.0011 indicates a statistically significant causal association. Results: Via IVW and WM, in directional MR, it was genetically predicted that zinc was nominally causally correlated with the risk of Parkinson's disease but not after Bonferroni correction test; alpha-tocopherol was nominally causally correlated with the risk of Amyotrophic lateral sclerosis (ALS) but not after Bonferroni correction test; furthermore, in reverse MR, it was genetically predicted that Alzheimer's disease was causally correlated with uric acid but not after Bonferroni correction test. These above findings were stable across sensitivity and pleiotropy analyses. Conclusions: Based on the current study, there is no authentic genetic causal association between OS biomarkers and neurodegenerative diseases. The complex relationship is required to be confirmed in future experimental research. [ABSTRACT FROM AUTHOR]

Background: Alcohol-induced osteoporosis is a significant health concern, impairing bone formation and enhancing resorption, thereby weakening skeletal integrity. This study examines the effects of palm vitamin E on bone histomorphometry in a male rat model of alcohol-induced osteoporosis. Methods: Three-month-old Sprague–Dawley rats were randomized into seven groups, with one baseline control group (BC) and six experimental groups undergoing a two-phase treatment. In the first month, the control group received normal saline, while experimental groups received intraperitoneal alcohol (3 g/kg) three times weekly. For the subsequent two months, alcohol treatment continued in one group (A), while others received olive oil (C), saline (AN), alpha-tocopherol (AA), or palm vitamin E (AE) orally. Results: Femur histomorphometric analysis post-sacrifice showed that alcohol exposure significantly decreased osteoblastic activity and impaired bone microarchitecture, evidenced by reduced Ob.S/BS, OS/BS, OV/BV, Tb.Th, BV/TV, and Tb.N, alongside increased Oc.S/BS, ES/BS, and Tb.Sp. Both alpha-tocopherol and palm vitamin E improved bone parameters, with palm vitamin E showing superior efficacy except in OV/BV. Conclusions: These findings suggest that palm vitamin E may offer a therapeutic benefit for mitigating alcohol-induced bone damage. [ABSTRACT FROM AUTHOR]

Abstract Water scarcity is a foremost environmental concern and is expected to hasten in the forthcoming years due to severe fluctuations in weather patterns worldwide. The present work was designed to explore the potential role of alpha-tocopherol (α-Toc), a form of vitamin E, on the morphological, physio-biochemical, and cellular antioxidant responses of two radish genotypes grown under drought conditions (38 ± 3% of field capacity). The individual and combined applications of α-Toc (100 ppm) were used as T0- Control, T1- Control + TF (TF-alpha-tocopherol), T2- Drought (D), and T3- D + TF with three replications. In general, drought conditions cause a marked reduction in, growth traits such as root length (RL), shoot dry weight (SDW), and shoot fresh weight (SFW). However, the sole and combined applications of α-Toc significantly enhanced the SDW, SFW, and RL in both radish genotypes. Drought stress causes a significant upsurge in hydrogen peroxide (H2O2) and lipid peroxidation (LPX) in leaves. At the same time, exogenous fertigation of α-Toc protects the membranes by reducing the level of LPX, enhancing antioxidants such as catalase (CAT) and peroxidase (POX) to scavenge the reactive oxygen species (ROS), and enhancing the osmolyte as total soluble proteins to maintain cell internal osmotic potential. Also, the α-Toc enhanced the photosynthetic pigments and significantly increased photosynthetic activity in the Early Milo (G2) as compared to Laal Pari (G1) genotype under drought, enhancing water use efficiency by maintaining transpiration rate and stomatal conductance. The α-Toc also regulates the beneficial inorganic ions (K+, Ca2+, and PO₄³⁻) in the shoots of both genotypes. Our present findings demonstrate the potential role of α-Toc in mitigating drought stress and infer that it can enhance plant growth under drought conditions.

BACKGROUND: Equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disease that primarily affects young, genetically predisposed horses that are deficient in vitamin E. Equine NAD/EDM has not previously been documented in Gypsy Vanner horses (GVs). OBJECTIVES: To evaluate: (1) the clinical phenotype, blood vitamin E concentrations before and after supplementation and pedigree in a cohort of GV horses with a high prevalence of neurologic disease suspicious for eNAD/EDM and (2) to confirm eNAD/EDM in GVs through postmortem evaluation. ANIMALS: Twenty-six GVs from 1 farm in California and 2 cases from the Midwestern U.S. METHODS: Prospective observational study on Californian horses; all 26 GVs underwent neurologic examination. Pre-supplementation blood vitamin E concentration was assessed in 17- GVs. Twenty-three were supplemented orally with 10 IU/kg of liquid RRR-alpha-tocopherol once daily for 28 days. Vitamin E concentration was measured in 23 GVs after supplementation, of which 15 (65%) had pre-supplementation measurements. Two clinically affected GVs from California and the 2 Midwestern cases had necropsy confirmation of eNAD/EDM. RESULTS: Pre-supplementation blood vitamin E concentration was ≤2.0 μg/mL in 16/17 (94%) of GVs from California. Post-supplementation concentration varied, with a median of 3.39 μg/mL (range, 1.23-13.87 μg/mL), but only 12/23 (52%) were normal (≥3.0 μg/mL). Normalization of vitamin E was significantly associated with increasing age (P = .02). Euthanized horses (n = 4) had eNAD/EDM confirmed at necropsy. CONCLUSIONS AND CLINICAL IMPORTANCE: GVs could have a genetic predisposition to eNAD/EDM. Vitamin E supplementation should be considered and monitored in young GVs.

Aims: Previous studies on the association between vitamin E and blood pressure (BP) levels are controversial. Our study aimed to evaluate the association between blood vitamin E (alpha-tocopherol and gamma-tocopherol) levels and systolic and diastolic BP in an adult population with diabetes and without diabetes. Methods: Our study data were obtained from a biomarker project of the Midlife in the United States (MIDUS) study. A total of 1068 subjects were included, and the associations between alpha-tocopherol and gamma-tocopherol levels and systolic and diastolic BP were further analyzed by smooth curve and multivariate linear regression analyses. Results: Our smooth curve analysis showed an almost linear correlation between blood vitamin E (alpha-tocopherol and gamma-tocopherol) levels and systolic and diastolic BP. Furthermore, we found that blood gamma-tocopherol levels were positively and independently associated with systolic BP (B=0.427, 95% CI 0.067-0.787, P=0.020) and diastolic BP (B=0.289, 95% CI 0.072-0.507, P=0.009) when the data were adjusted for age, gender, body mass index (BMI), ever smoked cigarettes regularly, number of years of consuming alcohol and regular exercise or activity for 20 minutes or more at least 3 times/week. Consistently, blood alpha-tocopherol levels were also positively associated with systolic BP (B=0.150, 95% CI 0.064-0.235, P=0.001) and diastolic BP (B=0.056, 95% CI 0.004-0.107, P=0.035) after these variables were adjusted. However, these significant relationships exist only in subjects without diabetes, but not in subjects with diabetes. Conclusions: We observed for the first time that blood vitamin E (alpha-tocopherol and gamma-tocopherol) levels were positively associated with systolic and diastolic BP in subjects without diabetes. [ABSTRACT FROM AUTHOR]

Although the Achilles tendon is the largest and strongest tendon in the body, healing of the Achilles tendon is the most common injury, and this process is difficult due to poor tendon circulation; moreover, the underlying mechanism has not been fully elucidated. In our study, we aimed to investigate the effects of pentoxifylline and alpha‐tocopherol administered separately or in combination on rats with Achilles tendon injury. Forty‐eight male Wistar rats weighing 230 ± 30 g were used in the study. The rats were randomly divided into eight groups of six animals each. Tendons were evaluated histopathologically and biomechanically. According to the statistical analysis, the vascularity density in the pentoxifylline group on day 14 was significantly greater than that in the other groups (p < 0.05). The collagen arrangement in the pentoxifylline and alpha‐tocopherol groups on day 14 was found to be firmer and smoother than that in the control group (p < 0.05). The collagen arrangement in the pentoxifylline group on day 28 was greater than that in the other groups (p < 0.05). The biomechanical results were significantly greater in all groups (p < 0.05). Pentoxifylline contributed to tendon healing both through neovascularization in the early period and by improving collagen orientation in the late period, while alpha‐tocopherol had a positive effect on collagen orientation in the early period. No beneficial effects were observed when pentoxifylline and alpha‐tocopherol were used together. We believe that further research is needed to understand the effects of this combination therapy on tendon healing. [ABSTRACT FROM AUTHOR]

Aging is physiologically associated with a decline in the function of the immune system and subsequent susceptibility to infections. Interferon-gamma (IFN-γ), a key element in the activation of cellular immunity, plays an important role in defense against virus infections. Decreased levels of IFN-γ in the elderly may explain their increased risk for viral infectious diseases such as COVID-19. There is accumulating evidence that ascorbic acid (vitamin C [VitC]) and α-tocopherol together help improve the function of the immune system in the elderly, control infections, and decrease the treatment duration. A SARS-CoV-2 strain was isolated from a patient and then cultured in the Vero cell line. The isolated and propagated virus was then inactivated using formalin and purified by the column chromatography. The inactivated SARS-CoV-2 was formulated in the Alum adjuvant combined with VitC or α-tocopherol and/or both of them. The vaccines were injected twice to young and aged C57BL/6 mice. Two weeks later, IFN-γ, IL-4, and IL-2 cytokines were assessed using ELISA Kits. Specific IgG and IgG1/IgG2a were assessed by an in-house ELISA. In addition, the expression of PD1 and TERT genes in the spleen tissue of the mice was measured using real-time PCR. IL-4 and IFN-γ cytokines showed a significant increase in both aged and young mice compared with the Alum-based vaccine. In addition, our results exhibited a significant decrease and increase in specific total IgG and the IgG2a/IgG1 ratio, respectively. Furthermore, the vaccine formulated in α-tocopherol + VitC led to decreased PD1 and increased TERT gene expression levels. In conclusion, our results demonstrated that α-tocopherol + VitC formulated in the inactivated SARS-CoV-2 vaccine led to a shift toward Th1, which may be due to their effect on the physiology of cells, especially aged ones and changing their phenotype toward young cells. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of Japanese dietary patterns on metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis. After excluding factors affecting the diagnosis of hepatic steatosis, 727 adults were analyzed as part of the Health Promotion Project. The dietary patterns of the participants were classified into rice, vegetable, seafood, and sweet based on their daily food intake. Liver stiffness measurements and controlled attenuation parameters were performed using FibroScan. Energy and nutrient intake were calculated using the Brief-type Self-administered Diet History Questionnaire. Univariate and multivariate analyses were used to identify the risk factors for liver fibrosis within the MASLD population. The vegetable group had significantly lower liver fibrosis indicators in the MASLD population than the rice group. The multivariate analysis identified a body mass index ≥ 25 kg/m2 (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.01–1.83; p = 0.047) and HOMA-IR ≥ 1.6 (OR, 3.18; 95% CI, 1.74–5.78; p < 0.001) as risk factors for liver fibrosis, and vegetable group membership was a significant low-risk factor (OR, 0.38; 95% CI, 0.16–0.88; p = 0.023). The multivariate analysis of nutrients in low-risk foods revealed high intake of α-tocopherol (OR, 0.74; 95% CI, 0.56–0.99; p = 0.039) as a significant low-risk factor for liver fibrosis. This study suggests that a vegetable-based Japanese dietary pattern, through the antioxidant effects of α-tocopherol, may help prevent liver fibrosis in MASLD and the development of MASLD. [ABSTRACT FROM AUTHOR]

Almond okara, a by-product of almond milk production, is rich in bioactive components, such as polyphenols, lipids, and alpha-tocopherol, making it a valuable functional food ingredient. This work aimed to investigate its composition while exploring two main aspects: (i) the impact of extraction time, solid-to-solvent ratio, ethanol concentration, and temperature on polyphenol recovery, and (ii) the quantification of okara's triglycerides (TG) and alpha-tocopherol contents. The polyphenols' optimal extraction conditions were 90 min, a 1:30 solid-to-solvent ratio (w/v), 50% ethanol, and 60 °C. These conditions achieved a total polyphenol yield of 523 mg GAE, tannin yield of 340 mg GAE, total flavonoid yield of 548 mg CE, and a total antioxidant capacity of 779 mg AAE per 100 g dry okara. The Peleg model effectively described the extraction kinetics. Additionally, TG levels, quantified by UHE/LPSFC-APCI-MS, in okara were comparable to those in almonds, and alpha-tocopherol levels, quantified by LC-UV, were 14,400 µg/100 g in almonds and 15,600 µg/100 g in okara. These findings highlight the potential of okara as a valuable resource, with a straightforward, scalable, and cost-effective solid-liquid extraction (SLE) method for polyphenols and a supercritical fluid extraction method for TG, for use in the functional food, nutraceutical, and cosmetic industries. [ABSTRACT FROM AUTHOR]

BackgroundPhosphorylated neurofilament heavy, a marker of neuroaxonal damage, is increased in horses with equine neuroaxonal dystrophy. However, the temporal dynamics of this biomarker during the post-natal risk period are not understood.ObjectiveTo measure serum and cerebrospinal fluid phosphorylated neurofilament heavy concentrations in juvenile foals across the post-natal window of susceptibility for equine neuroaxonal dystrophy.Study designCase-control in vivo experimental study.MethodsConcentrations of phosphorylated neurofilament heavy were measured using frozen serum and cerebrospinal fluid collected from 13 foals raised in a vitamin E deficient environment from 1 to 6 months of age. Four of these foals were produced by equine neuroaxonal dystrophy-affected dams, developed clinical signs consistent with equine neuroaxonal dystrophy and had a diagnosis confirmed by histopathology. The remaining nine foals, produced by healthy mares, were vitamin E depleted and remained clinically healthy. An additional cohort of foals, produced by healthy mares, were supplemented with vitamin E (α-tocopherol; α-TOH) from birth and sampled similarly.ResultsSerum α-TOH concentrations were significantly higher in vitamin E supplemented healthy foals. Serum phosphorylated neurofilament heavy concentrations did not differ significantly between groups at any time point. Cerebrospinal fluid phosphorylated neurofilament heavy concentrations increased with age in healthy vitamin E depleted foals (p

Vitamin E, present in both plant and animal-based foods, is a lipophilic compound with multifaceted biochemical functions. Its deficiency can lead to severe health consequences, while excessive intake may result in hypervitaminosis. Among tocopherols, Alpha-tocopherol stands out for its pharmacokinetic properties and potent antioxidant effects. It exerts significant influence on the immune, nervous, and cardiovascular systems, as well as on skin health. Notably, it plays a crucial role in preventing carcinogenesis. While Alpha-tocopherol garners attention, other tocopherol group members should not be overlooked, as advancements in science uncover their diverse biological impacts. In recent years, tocotrienols have emerged with distinct biochemical properties that profoundly affect human health.

Background: We investigated the individual and interaction effects of maternal plasma 훂‐ and ϒ‐tocopherol levels (vitamin E isomers) on child asthma and wheeze at age 8–9. Methods: Mother–child dyads were enrolled between 2006 and 2011 into the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) prenatal cohort. Maternal second‐trimester samples were analyzed for tocopherol and lipid concentrations. We assessed child asthma/wheeze using the International Study of Asthma and Allergies in Childhood (ISAAC) and other self‐reported Ent wheeze. In multivariable logistic regression analyses, we assessed associations between vitamin E isomers and child asthma/wheeze outcomes (n = 847 mother–child dyads) and tested for prespecified interaction terms. Results: Median cholesterol‐corrected tocopherol levels (interquartile range (IQR)) were 5.0 (4.3–5.7) and 0.8 (0.7–0.9) (umol/mmol) for 훂‐ and ϒ‐tocopherol, respectively. Associations between 훂‐tocopherol and asthma outcome variables were inverse but not statistically significant. In contrast, for ϒ‐tocopherol, associations were in the positive direction, but also nonsignificant. Interactions analysis between tocopherols did not reach statistical significance for any outcome. Among children of women with a history of asthma, the likelihood of ever asthma in the child appears to be decreasing with increasing maternal 훂‐tocopherol levels, whereas this trend was not observed among those without a history of asthma (p‐interaction =.05). Conclusion: We observed no associations for prenatal 훂‐ or ϒ‐tocopherol concentrations with child asthma/wheeze. We detected some evidence of effect modification by maternal asthma history in associations between 훂‐tocopherol and child asthma. [ABSTRACT FROM AUTHOR]

Introduction/Aim. Microencapsulation technology can be used for the protection of alpha-tocopherol from degradation in unfavorable environments and enhancement of bioavailability and shelf-life of vitamin E. The aim of this study was the synthesis and characterization of alginate microparticles for the oral delivery of a-tocopherol. Methods. Four different formulations of alpha-tocopherol loaded calcium alginate microparticles for oral delivery were synthesized by external ionotropic gelation method. The vitamin E content in microparticles was 0.5%, 1% and 2% (w/w); the vitamin E/sodium alginate ratio was 1:1 and 1:2. All microparticles were characterized by average particles size, swelling degree, vitamin E content, loading capacity, and encapsulation efficiency. Results. Spherically shaped microparticles with the diameter of 500 to 1000 µm were obtained after the drying process. The size and the swelling degree did not change significantly in 0.1 M HCL, while they were increased in base conditions of phosphate buffer of pH 6.8 and 7.4. Encapsulated vitamin E content was not significantly different between formulations (0.30 ± 0.010 - 0.60 ± 0.021 mg/mL). The loading capacities were in the range between 10 ± 0.11% and 20.45 ± 0.22%, while encapsulation efficiency percentages were between 18.94 ± 0.32% and 31.91 ± 0.41%. Conclusion. The optimum conditions for alpha-tocopherol encapsulation with the highest percentage of loading capacity and encapsulation efficacy were obtained using 1% sodium alginate, 2% calcium chloride, and vitamin E/polymer in the ratio 1:1. All four formulations showed the expected behavior in different mediums, which simulated gastrointestinal fluids in vivo (0.1 M HCL, phosphate buffer pH 6.8 and pH 7.4): gastroresistance, increasing in the size, and swelling degree in intestinal fluids. This emphasizes the use of alginate microparticles as a carrier for the oral delivery of vitamin E. [ABSTRACT FROM AUTHOR]

This review aimed to verify the effects of vitamin E supplementation on oxidative stress, inflammatory response, muscle damage, soreness, and strength in healthy adults after exercise. We searched the MEDLINE, EMBASE, SPORTDiscus, Cochrane CENTRAL, and Web of Science from inception to August 2023, with no language restrictions. We included randomized placebo-controlled trials evaluating the supplementation of vitamin E on the abovementioned outcomes after a bout of physical exercise in healthy participants (no restriction for publication year or language). Meta-analyses were conducted to compare vitamin E and placebo supplementations to obtain a 95% confidence interval (95%IC). Twenty studies were included (n=298 participants). The effect of supplementation was assessed between 0 h and 96 h after the exercise. Compared to placebo, vitamin E had no effects on lipid (95%IC= –0.09 to 0.42), protein (–2.44 to 3.11), SOD (–1.05 to 0.23), interleukin-6 (–0.18 to 1.16), creatine kinase (–0.33 to 0.27), muscle soreness (–1.92 to 0.69), and muscle strength (–1.07 to 0.34). Heterogeneity for the analyses on carbonyls, interleukin-6 (1 h and 3 h), and muscle soreness ranged between 70 to 94%. Supplementing with vitamin E should not be recommended to support the recovery process in healthy individuals after exercise, given the lack of efficacy in the analyzed variables following an exercise session. [ABSTRACT FROM AUTHOR]

AimsPrevious studies on the association between vitamin E and blood pressure (BP) levels are controversial. Our study aimed to evaluate the association between blood vitamin E (alpha-tocopherol and gamma-tocopherol) levels and systolic and diastolic BP in an adult population with diabetes and without diabetes.MethodsOur study data were obtained from a biomarker project of the Midlife in the United States (MIDUS) study. A total of 1068 subjects were included, and the associations between alpha-tocopherol and gamma-tocopherol levels and systolic and diastolic BP were further analyzed by smooth curve and multivariate linear regression analyses.ResultsOur smooth curve analysis showed an almost linear correlation between blood vitamin E (alpha-tocopherol and gamma-tocopherol) levels and systolic and diastolic BP. Furthermore, we found that blood gamma-tocopherol levels were positively and independently associated with systolic BP (B=0.427, 95% CI 0.067-0.787, P=0.020) and diastolic BP (B=0.289, 95% CI 0.072-0.507, P=0.009) when the data were adjusted for age, gender, body mass index (BMI), ever smoked cigarettes regularly, number of years of consuming alcohol and regular exercise or activity for 20 minutes or more at least 3 times/week. Consistently, blood alpha-tocopherol levels were also positively associated with systolic BP (B=0.150, 95% CI 0.064-0.235, P=0.001) and diastolic BP (B=0.056, 95% CI 0.004-0.107, P=0.035) after these variables were adjusted. However, these significant relationships exist only in subjects without diabetes, but not in subjects with diabetes.ConclusionsWe observed for the first time that blood vitamin E (alpha-tocopherol and gamma-tocopherol) levels were positively associated with systolic and diastolic BP in subjects without diabetes.

BackgroundThe association of different types of tocopherols (vitamin E) with cognition might vary by the APOEɛ4 allele status.ObjectiveWe examined the association of dietary tocopherols with cognitive decline among participants with and without the APOEɛ4 allele over a median of 12 years.Methods2,193 participants from the Chicago Health and Aging Project were included in the analyses. Global cognition was assessed in three-year cycles. We used a 144-item FFQ to assess dietary intakes of tocopherols and hME Sequenom mass-array platform to assess APOE genotype. We used linear mixed effects models to examine the relationship between tocopherol from food sources and global cognitive decline.ResultsThe mean baseline age was 74.1 (SD = 5.9) years. Among APOEɛ4 carriers, participants in the highest quintile of intakes of dietary vitamin E had a slower cognitive decline of 0.022 SDU (95% CI: 0.000, 0.043) compared to those in the lowest quintile. A higher intake of dietary α-tocopherol from food sources only was associated with slower cognitive decline in APOEɛ4 carriers (p for trend 0.002) but not among the non-carriers (p for trend 0.937). Among APOEɛ4 carriers, those in the highest quintile of intake of α-tocopherol had a 16.4% slower rate of decline of global cognition compared to those in the lowest quintile (β= 0.034, 95% CI: 0.013, 0.054).ConclusionsIndividuals consuming high α-tocopherol from food sources had slower cognitive decline among APOEɛ4 carriers. In older adults, different forms of vitamin E might moderate the relationship of APOEɛ4 with global cognition.

BACKGROUND: Omega-3 fatty acid and alpha-tocopherol supplementation reduces gastric ulcer formation in humans and rodents; however, efficacy of prevention in horses is unknown. Equine Omega Complete (EOC) is an oral supplement containing omega-3 fatty acids and alpha-tocopherol. HYPOTHESIS/OBJECTIVE: Determine if EOC supplementation prevents gastric ulcers and increases serum alpha-tocopherol concentrations in healthy horses. ANIMALS: Nine thoroughbred geldings; 5-13 years old. METHODS: Prospective randomized block design, repeated in crossover model. Horses were administered EOC, omeprazole, or water PO for 28 days. Horses underwent an established gastric ulcer induction protocol from days 21-28 via intermittent feed deprivation. Gastroscopies were performed on days 0, 21, and 28. Serum alpha-tocopherol concentrations were measured on days 0 and 28. The effects of treatment and time on ulcer grades were assessed with ordinal logistic regression, with significance at P-value

It is generally recognized that the main function of α-tocopherol (αToc), which is the most active form of vitamin E, is its antioxidant effect, while non-antioxidant effects have also been reported. We previously found that αToc ameliorates diabetic nephropathy via diacylglycerol kinase alpha (DGKα) activation in vivo, and the activation was not related to the antioxidant effect. However, the underlying mechanism of how αToc activates DGKα have been enigmatic. We report that the membrane-bound 67 kDa laminin receptor (67LR), which has previously been shown to serve as a receptor for epigallocatechin gallate (EGCG), also contains a novel binding site for vitamin E, and its association with Vitamin E mediates DGKα activation by αToc. We employed hydrogen-deuterium exchange mass spectrometry (HDX/MS) and molecular dynamics (MD) simulations to identify the specific binding site of αToc on the 67LR and discovered the conformation of the specific hydrophobic pocket that accommodates αToc. Also, HDX/MS and MD simulations demonstrated the detailed binding of EGCG to a water-exposed hydrophilic site on 67LR, while in contrast αToc binds to a distinct hydrophobic site. We demonstrated that 67LR triggers an important signaling pathway mediating non-antioxidant effects of αToc, such as DGKα activation. This is the first evidence demonstrating a membrane receptor for αToc and one of the underlying mechanisms of a non-antioxidant function for αToc.

Abstract The causal association between vitamin E status and osteoarthritis (OA) remains controversial in previous epidemiological studies. We employed a Mendelian randomization (MR) analysis to explore the causal relationship between circulating alpha-tocopherol levels (main forms of vitamin E in our body) and OA. The instrumental variables (IVs) of circulating alpha-tocopherol levels were obtained from a Genome-wide association study (GWAS) dataset of 7781 individuals of European descent. The outcome of OA was derived from the UK biobank. Two-sample MR analysis was used to estimate the causal relationship between circulating alpha-tocopherol levels and OA. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic in this work. The heterogeneity effect of instrumental IVs was detected by MR-Egger and IVW analyses. Sensitivity analysis was performed by removing single nucleotide polymorphism (SNP) one by one. Three SNPs (rs964184, rs2108622, and rs11057830) (P

Abstract Background Equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disease that primarily affects young, genetically predisposed horses that are deficient in vitamin E. Equine NAD/EDM has not previously been documented in Gypsy Vanner horses (GVs). Objectives To evaluate: (1) the clinical phenotype, blood vitamin E concentrations before and after supplementation and pedigree in a cohort of GV horses with a high prevalence of neurologic disease suspicious for eNAD/EDM and (2) to confirm eNAD/EDM in GVs through postmortem evaluation. Animals Twenty‐six GVs from 1 farm in California and 2 cases from the Midwestern U.S. Methods Prospective observational study on Californian horses; all 26 GVs underwent neurologic examination. Pre‐supplementation blood vitamin E concentration was assessed in 17‐ GVs. Twenty‐three were supplemented orally with 10 IU/kg of liquid RRR‐alpha‐tocopherol once daily for 28 days. Vitamin E concentration was measured in 23 GVs after supplementation, of which 15 (65%) had pre‐supplementation measurements. Two clinically affected GVs from California and the 2 Midwestern cases had necropsy confirmation of eNAD/EDM. Results Pre‐supplementation blood vitamin E concentration was ≤2.0 μg/mL in 16/17 (94%) of GVs from California. Post‐supplementation concentration varied, with a median of 3.39 μg/mL (range, 1.23‐13.87 μg/mL), but only 12/23 (52%) were normal (≥3.0 μg/mL). Normalization of vitamin E was significantly associated with increasing age (P = .02). Euthanized horses (n = 4) had eNAD/EDM confirmed at necropsy. Conclusions and Clinical Importance GVs could have a genetic predisposition to eNAD/EDM. Vitamin E supplementation should be considered and monitored in young GVs.

BackgroundIncreases in serum gamma-glutamyltransferase (GGT) activity have been reported in Thoroughbred (TB) racehorses and associated with maladaptation to training but the underlying etiology remains unknown.Hypothesis/objectivesClassify the etiology of high GGT syndrome in racing TBs by assessment of pancreatic enzymes, vitamin E concentrations, and both a candidate gene and whole genome association study. We hypothesized that a genetic variant resulting in antioxidant insufficiency or pancreatic dysfunction would be responsible for high GGT syndrome in TBs.AnimalsA total of 138 California racing TBs. Amylase: n = 31 affected (serum GGT activity ≥60 IU/L), n = 52 control (serum GGT activity

The causal association between vitamin E status and osteoarthritis (OA) remains controversial in previous epidemiological studies. We employed a Mendelian randomization (MR) analysis to explore the causal relationship between circulating alpha-tocopherol levels (main forms of vitamin E in our body) and OA. The instrumental variables (IVs) of circulating alpha-tocopherol levels were obtained from a Genome-wide association study (GWAS) dataset of 7781 individuals of European descent. The outcome of OA was derived from the UK biobank. Two-sample MR analysis was used to estimate the causal relationship between circulating alpha-tocopherol levels and OA. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic in this work. The heterogeneity effect of instrumental IVs was detected by MR-Egger and IVW analyses. Sensitivity analysis was performed by removing single nucleotide polymorphism (SNP) one by one. Three SNPs (rs964184, rs2108622, and rs11057830) (P < 5E−8) strongly associated with circulating alpha-tocopherol levels were used in this analysis. The IVW-random effect indicated no causal relationship between circulating alpha-tocopherol levels and clinically diagnosed OA (OR = 0.880, 95% CI 0.626, 1.236, P = 0.461). Similarly, IVW analysis showed no causal association between circulating alpha-tocopherol levels and self-reported OA (OR = 0.980, 95% CI 0.954, 1.006, P = 0.139). Other methods of MR analyses and sensitivity analyses revealed consistent findings. MR-Egger and IVW methods indicated no significant heterogeneity between IVs. The MR–Egger intercept showed no horizontal pleiotropic. The results of this linear Mendelian randomization study indicate no causal association between genetically predicted alpha-tocopherol levels and the progression of OA. Alpha-tocopherol may not provide beneficial and more favorable outcomes for the progression of OA. Further MR analysis based on updated GWASs with more IVs is required to verify the results of our study. [ABSTRACT FROM AUTHOR]