Comparative efficacy of tocotrienol and tocopherol (vitamin E) on atherosclerotic cardiovascular diseases in humans.

Objective: To compare the efficacy of tocotrienol and tocopherol in the management of patients with atherosclerotic cardiovascular diseases. METHODS: The systematic review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines 2020, and comprised literature search from 2002 till January 5, 2023, on PubMed, Google Scholar, Cochrane Library, Google, Wiley-Inter Science Library, Medline, SpringerLink, Taylor and Francis databases. The search was conducted using key words, such as: "tocopherol", "tocotrienol", "vitamin E", "dyslipidaemia", "cardiovascular diseases" "cardioprotective", "hypercholesterolemia" and "atherosclerosis" along with Boolean operators. Human clinical studies regarding the use of tocotrienol or tocopherol or comparison of its efficacy in patients having atherosclerosis, dyslipidaemia leading to cardiovascular diseases, and studies including details of efficacy of any of the four alpha, beta, gamma, delta isomers of tocopherol or tocotrienol were included. Pertinent data from the eligible studies was retrieved and reviewed. RESULTS: Of the 516 articles identified, 26 (5%) articles met eligibility criteria. Of them 5(19%) were subjected to detailed analysis. Tocotrienol showed significant anti-oxidant efficacy at (250 mg/d) by decreasing cholesterol and serum inflammatory biomarkers i.e C-reactive protein (40%), malondialdehyde (34%), gamma-glutamyl transferase (22%) (p<0.001). Total anti-oxidant status (TAS) levels raised 22% (p<0.001) and Inflammatory cytokines i.e resistin, interleukin (IL)-1, IL-12, Interferon-gamma were decreased 15-17% (p<0.05-0.01) respectively by tocotrienol. Several microRNA (miRNA-133a, miRNA-223, miRNA-214, miRNA-155) were modulated by δ-tocotrienol. Whereas, tocopherol showed heterogeneity of results by either decreasing or increasing the risk of mortality in atherosclerotic cardiovascular diseases. Conclusion: Compared to tocopherol, tocotrienol was found to be safe and potential candidate for improving cardiovascular health in the management of atherosclerotic cardiovascular diseases.

Is the use of Pentoxifylline and Tocopherol effective in the treatment of Osteoradionecrosis of the jaws or for the treatment of medicationosteonecrosis of the jaw? An overview.

PURPOSE: The aim of the present study was to determine the methodological quality of systematic reviews that evaluated the effectiveness of pentoxifylline and tocopherol (PENTO) in the treatment of osteoradionecrosis of the jaw (ORNJ) and medication-related osteonecrosis of the jaw (MRONJ). METHODS: Searches were performed in Databases including PubMed, Scopus, LILACS, DARE, Cochrane Library, and SIGLE through OpenGrey until March 2024, were evaluated by two independent reviewers to answer the following question: Is the use of PENTO protocol effective in the treatment of ORNJ or for the treatment of MRONJ? RESULTS: A total of 256 articles were initially identified; however, following the use of appropriate inclusion and exclusion criteria, five systematic reviews were identified for detailed analysis. The final study sample comprised 588 patients: 397 patients with ORN and 197 patients with MRONJ who were treated with PENTO. The total recovery of individuals who used the PENTO protocol was 62,2 % for ORN and 100 % for MRONJ, with a follow-up period of 1 month to 10 years. The methodological quality of the studies was assessed using the AMSTAR 2 tool, in which four were of low quality and 1 moderate quality. CONCLUSION: The treatment of ORN and MRONJ with pentoxifylline and tocopherol has shown good results in the studies presented, with a partial or total reduction in bone exposure. However, the low quality of the relevant reports highlights the need for primary and secondary studies with better methodological rigor to reduce bias and provide reassurance for this treatment option.

Development of α-Tocopherol Loaded PLGA Nanoparticles and Its Evaluation as a Novel Immune Adjuvant.

With the continuous development of preventive and therapeutic vaccines, traditional adjuvants cannot provide sufficient immune efficacy and it is of high necessity to develop safe and effective novel nanoparticle-based vaccine adjuvants. α-Tocopherol (TOC) is commonly used in oil-emulsion adjuvant systems as an immune enhancer, yet its bioavailability is limited by poor water solubility. This study aims to develop TOC-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TOC-PLGA NPs) to explore the potential of TOC-PLGA NPs as a novel nanoparticle-immune adjuvant. TOC-PLGA NPs are prepared by a nanoprecipitation method and their physicochemical properties are characterized. It is shown that TOC-PLGA NPs are 110.8 nm, polydispersity index value of 0.042, and Zeta potential of -13.26 mV. The encapsulation efficiency and drug loading of NPs are 82.57% and 11.80%, respectively, and the cumulative release after 35 days of in vitro testing reaches 47%. Furthermore, TOC-PLGA NPs demonstrate a superior promotion effect on RAW 264.7 cell proliferation compared to PLGA NPs, being well phagocytosed and also promoting antigen uptake by macrophages. TOC-PLGA NPs can strongly upregulate the expression of co-stimulatory surface molecules and the secretion of cytokines. In conclusion, TOC-PLGA NPs can be a novel vaccine adjuvant with excellent biocompatibility and significant immune-enhancing activity.

Alpha-Tocopherol Levels in Patients With Dentigerous Cysts: A Cross-Sectional Study.

Background Dentigerous cysts (DC) form due to fluid accumulation between the crown of the tooth and the reduced enamel epithelium. Due to the diverse clinical characteristics, such as ambiguity concerning their biological origins and the significance of timely diagnosis and detection of these lesions, researchers are presently motivated to undertake further investigations. The aim of the present study was to assess the amount of serum alpha-tocopherol in patients with DC and compare it with that of normal, healthy individuals. Methods A total sample size of n=34 was included in the current study. Group A, designated as the control group, comprised 17 randomly selected healthy subjects, while Group B, the DC diagnostic group, consisted of 17 patients. Blood samples were collected, and the concentration of vitamin E or alpha-tocopherol was evaluated and expressed in mg/mL. Results Compared to the mean vitamin E level in healthy controls (12.08 ± 1.92 mg/mL), patients with DC showed a statistically significant (p<0.0001) reduction in mean vitamin E levels (5.29 ± 1.01 mg/mL). Conclusion Patients with DC have lower levels of vitamin E than healthy individuals. The reduced concentration of vitamin E can have a role in the extension of cystic volume and thus have an impact on the aggressiveness of pathologic lesions. The therapeutic benefits of vitamin E supplementation in reducing the aggressiveness of DC should be evaluated in future research.

Comparative Study of Camellia oleifera Seed Oil on Chemical Constituents, Antioxidant Activities and Physicochemical Characteristics from Southern China.

Eleven kinds of Camellia oleifera seed oils (CSOs) were evaluated in terms of chemical constituents, antioxidant activities, acid value (AV) as well as peroxide value (POV). These CSOs contained abundant ß-sitosterol, squalene, α-tocopherol and phenolics, in which the squalene was the distinct constituent with the content between 45.8±0.8 and 184.1±5.5 mg/kg. The ß-sitosterol ranging from 143.7±4.8 to 1704.6±72.0 mg/kg contributed a considerable content to total accompaniments. Palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid were present in these CSOs, in which the dominant fatty acid was oleic acid with the content between 59.66±0.72 and 82.89±2.16 g/100 g. The AV ranged from 0.1±0.0 to 1.3±0.0 mg KOH/g, and the POV was between 0.1±0.0 and 1.0±0.0 g/100 g. These CSOs showed antioxidant activity based on DPPH and ABTS radical scavenging assay. Both α-tocopherol and ß-sitosterol contents showed a positive correlation with DPPH and ABTS values, respectively, while the α-tocopherol content showed a negative correlation with AV. These results suggested that CSO can be categorized into high oleic acid vegetable oil with abundant active constituents, of which the quality presented variation among different origins. These accompaniments may contribute to the delay of its quality deterioration.

Frost Damage Mitigation in Flowers and Fruitlets of Peach and Almond from the Application of a Multi-Attribute Approach Biostimulant.

To prevent frost damage in fruit trees, growers employ passive and active methods, and one of these second methods is the use of biostimulant compounds against abiotic stress. In this study, two trials were conducted to evaluate the effectiveness of a multi-attribute approach biostimulant-containing α-tocopherol, boron, and glycols, in peach ('UFO-4' cultivar) and almond ('Vairo' cultivar) trees. In a first trial, one-year-old shoots with flowers were collected after 24 h, 48 h, and 96 h of the biostimulant applications. Two different application rates of the product (1000 and 2000 cc ha-1) were tested and compared to an untreated control. In a second trial, one-year-old shoots with fruitlets were collected after 24 h of the biostimulant applications. In this case, only an application rate (2000 cc ha-1) was tested. In the two trials, the collected one-year-old shoots were subjected to different frost temperatures using a controlled environment chamber. The damage level was assessed by a morphological analysis of the flowers and fruitlets 96 h after each frost cycle simulation. The lethal temperatures (LT10, LT50, and LT90) of each treatment were calculated by probit analysis. The product applied 24 h and 48 h before the frost simulations significantly decreased the LT10 and LT50 in 1.5 °C in peach flowers, and 2.5 °C in almond flowers (a temperature reduction of 50% and 75%, respectively). These results were more consistent when the application volume was 2000 cc ha-1, instead of 1000 cc ha-1. Significant differences between treated and non-treated fruitlets were observed only in almond fruitlets, with LT10 and LT50 being 0.5 °C lower in treated fruitlets (20% reduction). In conclusion, the multi-attribute approach biostimulant applied 24 or 48 h before the frost reduced the mortality of peach and almond flowers, but its effectiveness to protect fruitlets after bloom was inconsistent.

An Eco-Friendly Supercritical CO2 Recovery of Value-Added Extracts from Olea europaea Leaves.

An eco-friendly approach towards the recovery of value-added extracts from olive tree leaves with the aid of supercritical CO2 at 30 MPa was carried out. The impact of extraction temperature (35-90 °C) and presence of co-solvents (ethanol, water, and aqueous ethanol) on the total phenolic, flavonoid, and pigment content, as well as oleuropein, hydroxytyrosol, tyrosol, and α-tocopherol content was determined. In addition, the antioxidant activity of extracts from tree leaves using DPPH, ABTS, and CUPRAC assays was investigated. The results of the study showed that the most effective supercritical CO2 extraction was at 90 °C with an addition of ethanol, which enabled the separation of extract with the highest content of tested compounds. Some of the highest recorded values were for oleuropein 1.9 mg/g, for carotenoids 5.3 mg/g, and for α-tocopherol 2.0 mg/g. Our results are expected to contribute to the efforts towards the valorization of olive leaves as a sustainable source of valuable compounds, and boost local economies as well as the interest of pharmaceutical, food, and cosmetic industries for novel food by-product applications.

Combination of legume proteins and arabinoxylans are efficient emulsifiers to promote vitamin E bioaccessibility during digestion.

The emulsification potential of plant-based emulsifiers, that is, pea (PPI) and lentil (LPI) proteins (4%), corn arabinoxylans (CAX, 1%), and legume protein-arabinoxylan mixtures (4% proteins + 0.15 or 0.9% CAX), was evaluated by assessing: the surface tension and potential of emulsifiers, emulsifier antinutritional contents, emulsion droplet size, emulsion physical stability, and vitamin E bioaccessibility from 10% oil-in-water emulsions. Tween 80 (2%) was used as a control. All emulsions presented small droplet sizes, both fresh and upon storage, except 4% LPI + 0.9% CAX emulsion that exhibited bigger droplet sizes (d(4,3) of approximately 18.76 µm vs 0.59 µm for the control) because of droplet bridging. Vitamin E bioaccessibility from emulsions stabilized with the combination of 4% PPI and either 0.15% or 0.9% CAX (28 ± 4.48% and 28.42 ± 3.87%, respectively) was not significantly different from that of emulsions stabilized with Tween 80 (43.56 ± 3.71%), whereas vitamin E bioaccessibility from emulsions stabilized with individual emulsifiers was significantly lower.

Rhodium-Catalyzed Enantioselective Intramolecular Hydroalkoxylation of Allenes and Application in the Total Synthesis of (R,R,R)-α-Tocopherol.

We report herein of a novel, enantioselective and rhodium- catalyzed cyclisation of allenyl alcohols towards chiral α-vinylic, cyclic ethers employing a rhodium/(R,R)-Me-ferrocelane catalyst. The corresponding chiral cyclic products were obtained in general high yield and enantioselectivities. The synthetic value of our obtained products was further exemplified by transformations of the allylic ether function. Furthermore, applying our newly developed method in our previously reported route towards the total synthesis of (R,R,R)-α-tocopherol, we were able to devise a significantly improved 2nd generation total synthesis with 12 steps in the longest linear sequence and an overall total yield of 24%.

Perceiving the functions of vitamin E through neutron and X-ray scattering.

Take your vitamins, or don't? Vitamin E is one of the few lipophilic vitamins in the human diet and is considered an essential nutrient. Over the years it has proven to be a powerful antioxidant and is commercially used as such, but this association is far from linear in physiology. It is increasingly more likely that vitamin E has multiple legitimate biological roles. Here, we review past and current work using neutron and X-ray scattering to elucidate the influence of vitamin E on key features of model membranes that can translate to the biological function(s) of vitamin E. Although progress is being made, the hundred year-old mystery remains unsolved.

Carbomer Hydrogels with Microencapsulated α-Tocopherol: Focus on the Biocompatibility of the Microcapsules, Topical Application Attributes, and In Vitro Release Study.

The microencapsulation of α-tocopherol based on the complex coacervation of low-molecular-weight chitosan (LMWC) and sodium lauryl ether sulphate (SLES) without harmful crosslinkers can provide biocompatible carriers that protect it from photodegradation and air oxidation. In this study, the influence of the microcapsule wall composition on carrier performance, compatibility with a high-water-content vehicle for topical application, and release of α-tocopherol were investigated. Although the absence of aldehyde crosslinkers decreased the encapsulation efficiency of α-tocopherol (~70%), the variation in the LMWC/SLES mass ratio (2:1 or 1:1) had no significant effect on the moisture content and microcapsule size. The prepared microcapsule-loaded carbomer hydrogels were soft semisolids with pseudoplastic flow behavior. The integrity of microcapsules embedded in the hydrogel was confirmed by light microscopy. The microcapsules reduced the pH, apparent viscosity, and hysteresis area of the hydrogels, while increasing their spreading ability on a flat inert surface and dispersion rate in artificial sweat. The in vitro release of α-tocopherol from crosslinker-free microcapsule-loaded hydrogels was diffusion-controlled. The release profile was influenced by the LMWC/SLES mass ratio, apparent viscosity, type of synthetic membrane, and acceptor medium composition. Better data quality for the model-independent analysis was achieved when a cellulose nitrate membrane and ethyl alcohol 60% w/w as acceptor medium were used.

Effects of derivatization coupled with GC-FID analysis of cholesterol in some bakery products.

Cholesterol analysis by derivatization technique is a time consuming, costly, and complex process while analyzing cholesterol without derivation is a simple, and quick method.Researchers analyzed cholesterol using both derivatization and non-derivatization techniques successfully. The objective of this study was to investigate the effect of derivatization in cholesterol analysis particularly on bakery goods.The retention time of non-derivatized cholesterol (11.62 min) and non-derivatized α-tocopherol standard (11.60 min) was very close in HP-5 capillary GC column andthey eluted together while injected as mixed standard. As a result, cholesterol content determined by non-derivatized technique could be overestimated due to the presence of α-tocopherol inbakery products. The peak resolution (Rs) between derivatized cholesterol and derivatized α-tocopherol standard using the appliedgradient GC condition was 3.1 which is well separated (>1.5) based on AOAC guidelines. The derivatized gas chromatographic cholesterol analysis method was verified by limit of detection (LOD; 0.03 mg/100 g), limit of quantification (LOQ; 0.08 mg/100 g), linearity (R2; 0.999),precision (repeatability: relative standard deviation (RSD) 1.5 %; reproducibility: RSD 1.9 %), and accuracy (102.1 % recovery). The verified cholesterol analysis method was subsequently applied to determine cholesterol content in selected bakery items, yielding a range of 2.76 ± 0.06 mg/100 g (chrysanthemum bread) to 114.26 ± 4.72 mg/100 g (castella).

Oxidative stress and neurodegenerative diseases: a bidirectional Mendelian randomization study.

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.

Synergistic integration of deep learning with protein docking in cardiovascular disease treatment strategies.

This research delves into the exploration of the potential of tocopherol-based nanoemulsion as a therapeutic agent for cardiovascular diseases (CVD) through an in-depth molecular docking analysis. The study focuses on elucidating the molecular interactions between tocopherol and seven key proteins (1O8a, 4YAY, 4DLI, 1HW9, 2YCW, 1BO9 and 1CX2) that play pivotal roles in CVD development. Through rigorous in silico docking investigations, assessment was conducted on the binding affinities, inhibitory potentials and interaction patterns of tocopherol with these target proteins. The findings revealed significant interactions, particularly with 4YAY, displaying a robust binding energy of -6.39 kcal/mol and a promising Ki value of 20.84 µM. Notable interactions were also observed with 1HW9, 4DLI, 2YCW and 1CX2, further indicating tocopherol's potential therapeutic relevance. In contrast, no interaction was observed with 1BO9. Furthermore, an examination of the common residues of 4YAY bound to tocopherol was carried out, highlighting key intermolecular hydrophobic bonds that contribute to the interaction's stability. Tocopherol complies with pharmacokinetics (Lipinski's and Veber's) rules for oral bioavailability and proves safety non-toxic and non-carcinogenic. Thus, deep learning-based protein language models ESM1-b and ProtT5 were leveraged for input encodings to predict interaction sites between the 4YAY protein and tocopherol. Hence, highly accurate predictions of these critical protein-ligand interactions were achieved. This study not only advances the understanding of these interactions but also highlights deep learning's immense potential in molecular biology and drug discovery. It underscores tocopherol's promise as a cardiovascular disease management candidate, shedding light on its molecular interactions and compatibility with biomolecule-like characteristics.

Metabolism of 11'-α- and 11'-γ-Tocomonoenols in HepG2 Cells Favors the γ-Congener and Results Predominantly in Carboxymethylbutyl-Hydroxychromans.

SCOPE: Tocomonoenols (T1) are little-known vitamin E derivatives naturally occurring in foods. Limited knowledge exists regarding the cellular uptake and metabolism of α-tocomonoenol (αT1) and none about that of γ-tocomonoenol (γT1). METHODS AND RESULTS: The study investigates the cytotoxicity, uptake, and metabolism of αT1 and γT1 in HepG2 cells compared to the α- and γ-tocopherols (T) and -tocotrienols (T3). None of the studied tocochromanols are cytotoxic up to 100 µmol L-1. The uptake of the γ-congeners is significantly higher than that of the corresponding α-forms, whereas no significant differences are observed based on the degree of saturation of the sidechain. Carboxymethylbutyl-hydroxychromans (CMBHC) are the predominant short-chain metabolites of all tocochromanols and conversion is higher for γT1 than αT1 as well as for the γ-congeners of T and T3. The rate of metabolism increases with the number of double bonds in the sidechain. The rate of metabolic conversion of the T1 is more similar to tocopherols than to that of the tocotrienols. CONCLUSION: This is the first evidence that both αT1 and γT1 follow the same sidechain degradation pathway and exert similar rates of metabolism than tocopherols. Therefore, investigation into the biological activities of tocomonoenols is warranted.

The interaction between lipid oxidation and the Maillard reaction model of lysine-glucose on aroma formation in fragrant sesame oil.

The formation mechanism behind the sophisticated aromas of sesame oil (SO) has not been elucidated. The interaction effects of the Maillard reaction (MR) and lipid oxidation on the aroma formation of fragrant sesame oil were investigated in model reaction systems made of l-lysine (Lys) and d-glucose (Glc) with or without fresh SO (FSO) or oxidized SO (OSO). The addition of OSO to the Lys-Glc model increased the MR browning at 294 nm and 420 nm and enhanced the DPPH radical scavenging activity greater than the addition of FSO (p < 0.05). The presence of lysine and glucose inhibited the oxidation of sesame oil, reduced the loss of γ-tocopherol, and facilitated the formation of sesamol (p < 0.05). The Maillard-lipid interaction led to the increased concentrations of some of the alkylpyrazines, alkylfurans, and MR-derived ketones and acids (p < 0.05) while reducing the concentrations of other pyrazines, lipid-derived furans, aliphatic aldehydes, ketones, alcohols, and acids (p < 0.05). The addition of FSO to the MR model enhanced the characteristic roasted, nutty, sweet, and fatty aromas in sesame oil (p < 0.05), while excessive lipid oxidation (OSO) brought about an unpleasant oxidized odor and reduced the characteristic aromas. This study helps to understand the sophisticated aroma formation mechanism in sesame oil and provides scientific instruction for precise flavor control in the production of sesame oil.

Different Roles of Tocopherols and Tocotrienols in Chemoprevention and Treatment of Prostate Cancer.

The vitamin E family contains α-tocopherol (αT), ßT, γT, and δT and α-tocotrienol (TE), ßTE, γTE, and δTE. Research has revealed distinct roles of these vitamin E forms in prostate cancer (PCa). The ATBC trial showed that αT at a modest dose significantly decreased PCa mortality among heavy smokers. However, other randomized controlled trials including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) indicate that supplementation of high-dose αT (≥400 IU) does not prevent PCa among nonsmokers. Preclinical cell and animal studies also do not support chemopreventive roles of high-dose αT and offer explanations for increased incidence of early-stage PCa reported in the SELECT. In contrast, accumulating animal studies have demonstrated that γT, δT, γTE, and δTE appear to be effective for preventing early-stage PCa from progression to adenocarcinoma in various PCa models. Existing evidence also support therapeutic roles of γTE and its related combinations against advanced PCa. Mechanistic and cell-based studies show that different forms of vitamin E display varied efficacy, that is, δTE ≥ γTE > δT ≥ γT >> αT, in inhibiting cancer hallmarks and enabling characteristics, including uncontrolled cell proliferation, angiogenesis, and inflammation possibly via blocking 5-lipoxygenase, nuclear factor κB, hypoxia-inducible factor-1α, modulating sphingolipids, and targeting PCa stem cells. Overall, existing evidence suggests that modest αT supplement may be beneficial to smokers and γT, δT, γTE, and δTE are promising agents for PCa prevention for modest-risk to relatively high-risk population. Despite encouraging preclinical evidence, clinical research testing γT, δT, γTE, and δTE for PCa prevention is sparse and should be considered.

Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by MF59 and AS03-like Adjuvants.

MF59 and AS03 are squalene emulsion-based vaccine adjuvants with similar compositions and droplet sizes. Despite their broad use in licensed influenza vaccines, few studies compared their adjuvant effects and action mechanisms side by side. Considering the majority of adjuvants act on dendritic cells (DCs) to achieve their adjuvant effects, this study compared MF59 and AS03-like adjuvants (AddaVax and AddaS03, respectively) to enhance antigen uptake, DC maturation, ovalbumin (OVA) and seasonal influenza vaccine-induced immune responses. Considering MF59 was reported to activate MyD88 to mediate its adjuvant effects, this study also investigated whether the above-explored adjuvant effects of AddaVax and AddaS03 depended on MyD88. We found AddaVax more potently enhanced antigen uptake at the local injection site, while AddaS03 more potently enhanced antigen uptake in the draining lymph nodes. AddaS03 but not AddaVax stimulated DC maturation. Adjuvant-enhanced antigen uptake was MyD88 independent, while AddaS03-induced DC maturation was MyD88 dependent. AddaVax and AddaS03 similarly enhanced OVA-induced IgG and subtype IgG1 antibody responses as well as influenza vaccine-induced hemagglutination inhibition antibody titers, whileAddaS03 more potently enhanced OVA-specific IgG2c antibody responses. Both adjuvants depended on MyD88 to enhance vaccine-induced antibody responses, while AddaVax depended more on MyD88 to achieve its adjuvant effects. Our study reveals similarities and differences of the two squalene emulsion-based vaccine adjuvants, contributing to our improved understanding of their action mechanisms.

No genetic causal association between circulating alpha-tocopherol levels and osteoarthritis, a two-sample Mendelian randomization analysis.

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.

Current insights into equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy.

Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is an inherited neurodegenerative disease associated with vitamin E deficiency in the first year of life. It is the second most common cause of spinal ataxia in horses euthanized for neurologic disease. Equine NAD/EDM is characterized by neurologic signs including a symmetric proprioceptive ataxia (> grade 2/5) and a wide-base stance at rest. There are currently no antemortem tests for eNAD/EDM in any breed. Conclusive diagnosis requires postmortem histologic evaluation of the brainstem and spinal cord at necropsy. Research studies on antemortem biomarkers and genetic testing are ongoing. The development of a genetic test for eNAD/EDM would have widespread impact, even if it were breed specific. Currently, the best approach to eNAD/EDM is to focus on preventing cases by providing pregnant mares and foals with access to pasture. Alternatively, dams' diets can be supplemented with high doses of water-soluble RRR-α-tocopherol during the last trimester of gestation, with continued supplementation of foals through the first two years of life. It is important to measure horses' baseline serum vitamin E levels prior to supplementing. While considered generally safe, oversupplementation of vitamin E is possible and can lead to coagulopathies.