Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*

OBJECTIVE: To prepare vitamin E polyethylene glycol 1000 succinate (TPGS)-modified insulin-loaded liposomes (T-LPs/INS) and evaluate its safety, corneal permeability, ocular surface retention and pharmacokinetics in rabbit eyes. METHODS: The safety of the preparation was investigated in human corneal endothelial cells (HCECs) using CCK8 assay and live/dead cell staining. In the ocular surface retention study, 6 rabbits were randomized into 2 equal groups for application of fluorescein sodium dilution or T-LPs/INS labeled with fluorescein in both eyes, which were photographed under cobalt blue light at different time points. In the cornea penetration test, another 6 rabbits divided into 2 groups for application of Nile red diluent or T-LPs/INS labeled with Nile red in both eyes, after which the corneas were harvested for microscopic observation. In the pharmacokinetic study, 2 groups of rabbits (n=24) were treated with eye drops of T-LPs/INS or insulin, and the aqueous humor and cornea were collected at different time points for measurement of insulin concentrations using enzyme linked immunosorbent assay. DAS2 software was used to analyze the pharmacokinetic parameters. RESULTS: The prepared T-LPs/INS showed good safety in cultured HCECs. Corneal permeability assay and fluorescence tracer ocular surface retention assay demonstrated a significantly higher corneal permeability of T-LPs/INS with a prolonged drug residence in the cornea. In the pharmacokinetic study, insulin concentrations in the cornea at 6, 15, 45, 60, and 120 min (P < 0.01) and in the aqueous humor at 15, 45, 60, and 120 min after dosing were significantly higher in T-LPs/INS group. The changes in insulin concentrations in the cornea and aqueous humor were consistent with a two-compartment model in T-LPs/INS group and with the one-compartment model in the insulin group. CONCLUSION The prepared T-LPs/INS shows an improved corneal permeability, ocular surface retention capacity and eye tissue concentration of insulin in rabbits.
Humans ; Animals ; Rabbits ; Insulin ; Liposomes ; Endothelial Cells ; Lipopolysaccharides ; Vitamin E ; Cornea ; Fluorescein

OBJECTIVE: To explore the association of maternal periconceptional folic acid or multiple micronutrients supplementation during periconceptional period and the serum vitamin E (Vit.E) concentration in the 1st trimester of gestational period. METHODS: A retrospective cohort study was conducted based on the prenatal health care system and clinical laboratory information system. Totally, 22 171 pregnant women who had their prenatal health care and gave birth in Tongzhou Maternal & Child Health Hospital of Beijing from Jan. 2016 to Dec. 2018 were recruited. The usage patterns of nutritional supplements [folic acid (FA) or multiple micronutrients (MM)] during periconceptional period were independent variables, and serum Vit.E concentration and serum Vit.E concentration≥11.2 mg/L in the 1st trimester of gestational period were outcome variables for generalized linear regression model and Logistic regression model, respectively, to analyze the relationships between the independent and outcome variables. RESULTS: The range of the serum Vit.E concentration in the 1st trimester of gestational period was 5.2-24.0 mg/L, and the median concentration was 10.1 (8.8-11.6) mg/L; the excess rate of the serum Vit.E of those who took MM supplementation was 0.3%, and the rates for the groups of FA only or no nutritional supplements used were both 0.1%. Compared with women without nutritional supplement or the women taking FA, the women who took MM had higher serum Vit.E levels in the 1st trimester of gestational period (both P < 0.05). The women taking FA or MM initiated before the conception showed that the serum Vit.E concentration in the 1st trimester of gestational period was higher than that after the conception (P < 0.05), and the serum Vit.E concentration of women who took regularly was higher than that of irregular taking (P < 0.05); with taking compliance elevated, the serum Vit.E concentration of the two groups of women taking FA or MM increased (P < 0.05). The risk of serum Vit.E concentration≥11.2 mg/L among the women taking MM was higher than that of the women without nutritional supplements or taking FA only [odds ratio (OR)=1.36, 95% confidence interval (95%CI): 1.21-1.53; OR=1.39, 95%CI: 1.31-1.48)]; women who took FA or MM showed a lower risk for serum Vit.E concentration≥11.2 mg/L of taking it after the conception than before, the ORs (95%CI) were 0.86 (95%CI: 0.77-0.96) and 0.88 (95%CI: 0.81-0.95), respectively; the women taking the two supplements regularly had higher risk for serum Vit.E concentration≥11.2 mg/L than irregular taking, the ORs (95%CI) were 1.16 (95%CI: 1.05-1.29) and 1.13 (95%CI: 1.04-1.22) for FA and MM users, respectively; with the compliance increasing, the women taking MM had a higher risk of serum Vit.E levels≥11.2 mg/L in the 1st trimester [OR (95%CI) was 1.10 (1.07-1.14)], but for FA users, the OR (95%CI) was 1.04(1.00-1.08). CONCLUSION Vit.E nutritional status in women in early gestational period in Beijing was generally good, and the excess rate of serum Vit.E was higher in women who took MM during periconceptional period than those without nutritional supplement or taking FA only, suggesting that women need to consider their own Vit.E nutritional status to choose the type of nutritional supplements during periconceptional period, so as to avoid related health hazards.
Child ; Dietary Supplements ; Female ; Folic Acid ; Humans ; Pregnancy ; Retrospective Studies ; Vitamin E ; Vitamins

OBJECTIVES: To investigate the levels of fat-soluble vitamins A, D, and E in children with obesity and their influencing factors. METHODS: A total of 273 children with obesity who attended the Department of Clinical Nutrition, Xi'an Children's Hospital, from January 2019 to April 2021 were enrolled as the obesity group. A total of 226 children with normal body weight who underwent physical examination during the same period were enrolled as the control group. Anthropometric parameters and body composition were measured for both groups, and the serum concentrations of vitamins A, D, and E were also measured. RESULTS: Compared with the control group, the obesity group had significantly higher serum levels of vitamin A [(1.32±0.21) μmol/L vs (1.16±0.21) μmol/L, P<0.001] and vitamin E [(9.3±1.4) mg/L vs (8.3±1.2) mg/L, P<0.001] and a significant reduction in the level of 25-hydroxyvitamin D [(49±22) nmol/L vs (62±24) nmol/L, P<0.001]. In the obesity group, the prevalence rates of marginal vitamin A deficiency, vitamin D deficiency/insufficiency, and vitamin E insufficiency were 5.5% (15/273), 56.8% (155/273), and 4.0% (11/273), respectively. After adjustment for body mass index Z-score and waist-to-height ratio, serum vitamin A level was positively correlated with age (P<0.001), while vitamins E and 25-hydroxyvitamin D levels were negatively correlated with age in children with obesity (P<0.001). After adjustment for age, the serum levels of vitamin A, vitamin E and 25-hydroxyvitamin D were not correlated with degree of obesity, percentage of body fat, and duration of obesity in children with obesity, while the serum levels of vitamins A and E were positively correlated with waist-to-height ratio (P<0.001). CONCLUSIONS There are higher serum levels of vitamins A and E in children with obesity, especially in those with abdominal obesity, while serum vitamin D nutritional status is poor and worsens with age. Therefore, vitamin D nutritional status should be taken seriously for children with obesity, and vitamin D supplementation should be performed when necessary.
Calcifediol ; Child ; Humans ; Pediatric Obesity ; Vitamin A ; Vitamin D ; Vitamin E ; Vitamins

OBJECTIVE: To investigate the incidence of hypertension disorders complicating pregnancy (HDCP) and vitamin E (VE) nutritional status among pregnant women in Beijing, and to determine the relationship between serum VE concentration in the first trimester of pregnancy and the risk of developing HDCP. METHODS: A retrospective cohort study was performed including 22 283 cases of pregnant women who underwent singleton deliveries in Tongzhou Maternal & Child Health Hospital of Beijing from January 2016 through December 2018 and received tests of serum VE concentrations in the first trimester of pregnancy. Nonconditional Logistic regression model was used to analyze the association between serum VE concentration levels and the risk of developing HDCP. RESULTS: The total incidence of HDCP was 5.4%, with the incidence of gestational hypertension around 2.1% and the incidence of preeclampsia-eclampsia around 3.3%. The median concentration of serum VE in early pregnancy was 10.1 (8.8-11.6) mg/L, and 99.7% of the participants had normal serum VE concentrations. The incidence of gestational hypertension and that of preeclampsia-eclampsia had been annually increasing in three years; a linear-by-linear association had also been observed between the serum VE concentrations and the years of delivery. According to the results of the univariable and the multivariable Logistic regression analyses, higher risks of developing HDCP had been observed among women with higher serum VE concentrations. Compared to those with serum VE concentrations in interquartile range (P₂₅-P₇₅) of all the participants, the women whose serum VE concentrations above P₇₅ were at higher risks to be attacked by HDCP (OR = 1.34, P < 0.001), gestational hypertension (OR = 1.39, P = 0.002), or preeclampsia-eclampsia (OR = 1.34, P = 0.001), as suggested by the results of the multivariable Logistic regression model analyses. In addition, the women with serum VE concentrations of 11.2 mg/L or above had a significantly higher risk of developing HDCP than those whose serum VE concentrations of P₄₀-P₆₀ of all the participants, and this risk grew higher as serum VE concentrations in the first trimester of pregnancy increased. CONCLUSION Women in Beijing are at good nutritional status. From January 2016 to December 2018, the incidence of HDCP increased with serum VE concentration level, and serum VE concentration of 11.2 mg/L is an indicator of an increased risk of developing HDCP, suggesting that pregnant women should take nutritional supplements containing VE carefully.
Female ; Humans ; Hypertension, Pregnancy-Induced ; Pre-Eclampsia ; Pregnancy ; Pregnancy Trimester, First ; Retrospective Studies ; Vitamin E

OBJECTIVE: To explore the protective effect of vitamin E (VE) against radiation injury of hippocampal neurons in mice and explore the possible mechanism. METHODS: Cultured HT-22 and U251 cells with or without exposure to 8 Gy irradiation were treated with VE (200 μmol/L for 24 h), ferroptosis inhibitor (ferrostatin-1, 5 μmol/L for 24 h), apoptosis inhibitor (ZVAD-FMK, 2 μmol/L), or necroptosis inhibitor (100 μmol/L). MTT assay was used to evaluate the cell viability after the treatments, and reduced glutathione (GSH), malondialdehyde (MDA), lipid reactive oxygen species (lipid ROS), and intracellular iron ion levels were detected for assessment of ferroptosis. The mice exposed to 16 Gy irradiation with or without vitamin E (500 U/kg) treatment for 6 weeks were assessed for behavioral changes and cognitive functions using Morris water maze test. RESULTS: Treatment with VE significantly promoted the cell survival following irradiation in HT-22 cells ( < 0.05) but not in U251 cells ( > 0.05). Ferrostatin-1, but not ZVAD or the necroptosis inhibitor, promoted the survival of HT-22 cells following the irradiation. Exposure to irradiation significantly increased ferroptosis-related oxidative stress level in HT-22 cells, manifested by decreased GSH level and increased MDA, lipid ROS and intracellular iron ion levels ( < 0.05); treatment with VE and ferrostatin-1 both obviously reversed radiation-induced ferroptosis-related oxidative stress in the cells ( < 0.05). In Morris water maze test, the mice with radiation exposure showed obviously increased exploration time and distance ( < 0.05), which were significantly decreased after treatment with VE ( < 0.05). CONCLUSIONS Vitamin E reduces radiation injury by inhibiting ferroptosis in the hippocampal neurons in mice.
Animals ; Ferroptosis ; Hippocampus ; Mice ; Neurons ; Radiation Injuries ; Vitamin E

BACKGROUND/OBJECTIVES: The leaves of Moringa oleifera (MO) and Moringa stenopetala (MS) commonly grown in Ethiopia possess potential nutritional and medicinal value. The aim of this study was to evaluate the nutritional and functional characteristics of the dried leaf powder from two Moringa species to develop sustainable nutritional supplements for Ethiopians from locally grown plant sources. SUBJECTS/METHODS: Freshly harvested and air-dried MO and MS leaves were authenticated and the nutritional contents, such as protein, ash, lipids, and selected vitamins and minerals, were analyzed using standard analytical procedures. Amino acid compositions were also determined by an amino acid analyzer. Nine-week-old mice were randomly divided into four groups to investigate the anti-obesity effects of Moringa. The first group was fed a basal diet, the second group a high-fat diet, and the others were fed a high-fat diet containing 0.1% Moringa leaf powder from each species. After seven weeks, serum indices related to lipid profiles from each mouse were analyzed. RESULTS: The present study revealed high protein (28–29%) and ash (7–11%) contents. Glutamic acid, aspartic acid, proline, and leucine were the most abundantly found amino acids in both species. The predominant minerals in the leaf powder were calcium (826–1,530 mg/100 g), potassium (794–904 mg/100 g), and magnesium (286-431 mg/100 g). Pyridoxine (475.06 mg/100 g) and vitamin E (34.2 mg/100 g) were found only in MS. Niacin was found only in MO at 32.21 mg/100 g, whereas ascorbic acid was found in both species (3.89 and 6.19 mg/100 g dry weight for MO and MS, respectively). The results of the animal study showed that mice on a high-fat diet containing 0.1% MO leaf powder alleviated the elevation of cholesterol, triglycerides, and low-density lipoprotein cholesterol induced by the high fat diet. MO was more effective than MS in preventing hypercholesterolemia and fat deposition. CONCLUSIONS: The findings in this work confirmed that Moringa leaves of both MO and MS possessed high nutritional value but MO was better at preventing the harmful effects of the high-fat diet than MS.
Amino Acids ; Animals ; Ascorbic Acid ; Aspartic Acid ; Calcium ; Cholesterol ; Diet ; Diet, High-Fat ; Ethiopia ; Glutamic Acid ; Hypercholesterolemia ; Leucine ; Lipoproteins ; Magnesium ; Mass Screening ; Mice ; Minerals ; Miners ; Moringa oleifera ; Moringa ; Niacin ; Nutritive Value ; Plants ; Potassium ; Proline ; Pyridoxine ; Triglycerides ; Vitamin E ; Vitamins

OBJECTIVE: Dysmenorrhea is one of the most common problems for women, especially during their reproductive age. Various studies have examined the effects of vitamins D and E and ginger supplements. This study aimed to investigate the individual effects of each of these supplements on dysmenorrhea. METHODS: This single-blind clinical trial was conducted in 2016 on students aged 18 to 25 years who complained of mild to severe dysmenorrhea. The participants were randomly assigned into 4 groups: vitamin D, vitamin E, ginger, and placebo. The effects of the supplements on the severity of dysmenorrhea were evaluated in 2 successive cycles using the visual analog scale (VAS) and a questionnaire. RESULTS: Initially, 240 female students were enrolled in the study; thereafter, 40 students were excluded from the study owing to follow-up loss. The average VAS score for dysmenorrhea in the entire study population was 7.13±0.80 before the intervention; the mean VAS score after the first and second months of supplement use was 5.37±1.51 and 4.93±1.48, respectively. The highest reduction in pain severity was observed in the ginger group (F=74.54, P<0.001). CONCLUSION: Vitamin D, vitamin E, and ginger significantly reduced the severity of dysmenorrhea, with ginger having the most significant effect followed by vitamin D and vitamin E. Given the low risk of these supplements, more studies must be conducted on their use as opposed to analgesics.
Analgesics ; Dysmenorrhea ; Female ; Follow-Up Studies ; Ginger ; Humans ; Menstrual Cycle ; Visual Analog Scale ; Vitamin D ; Vitamin E ; Vitamins

Hesperetin, an abundant bioactive component of citrus fruits, is poorly water-soluble, resulting in low oral bioavailability. We developed new formulations to improve the water solubility, antioxidant activity, and oral absorption of hesperetin. Two nano-based formulations were developed, namely hesperetin-TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) micelles and hesperetin-phosphatidylcholine (PC) complexes. These two formulations were prepared by a simple technique called solvent dispersion, using US Food and Drug Administration (FDA)-approved excipients for drugs. Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were used to characterize the formulations' physical properties. Cytotoxicity analysis, cellular antioxidant activity assay, and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations. The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility, which increased to 21.5- and 20.7-fold, respectively. The hesperetin-TPGS micelles had a small particle size of 26.19 nm, whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm. In addition, the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2- and 3.9-fold, respectively. Importantly, the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration (C_max) from 2.64 μg/mL to 20.67 and 33.09 μg/mL and also increased the area under the concentration-time curve of hesperetin after oral administration to 16.2- and 18.0-fold, respectively. The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin, indicating these formulations' potential applications in drugs and healthcare products.
Administration, Oral ; Animals ; Antioxidants/chemistry* ; Biological Availability ; Calorimetry, Differential Scanning ; Dogs ; Dose-Response Relationship, Drug ; Drug Carriers ; Female ; Hep G2 Cells ; Hesperidin/chemistry* ; Humans ; Light ; Madin Darby Canine Kidney Cells ; Micelles ; Phosphatidylcholines/chemistry* ; Polyethylene Glycols/chemistry* ; Rats ; Rats, Sprague-Dawley ; Scattering, Radiation ; Solubility ; Solvents ; Vitamin E/chemistry* ; Water/chemistry* ; alpha-Tocopherol/chemistry*

PURPOSE: Vitamin D is a potent immunomodulator. However, its role in the pathogenesis of allergic rhinitis is unclear. METHODS: The aim of this study was to evaluate the antiallergic effect of intranasally applied vitamin D in an allergic rhinitis mouse model. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and alum before they were intranasally challenged with OVA. Then, they were intranasally administered 1, 25-dihydroxyvitamin D3 (0.02 μg) or solvent. Allergic symptom scores, eosinophil infiltration, cytokine mRNA levels (interleukin [IL]-4, IL-5, IL-10, IL-13 and interferon-γ) in the nasal tissue, and serum total immunoglobulin E (IgE) and OVA-specific IgE, IgG1, and IgG2a were analyzed and compared with negative and positive control groups. Cervical lymph nodes (LNs) were harvested for flow cytometry analysis and cell proliferation assay. RESULTS: In the treatment group, allergic symptom scores, eosinophil infiltration, and mRNA levels of IL-4 and IL-13 were significantly lower in the nasal tissue than in the positive control group. The IL-5 mRNA level, serum total IgE, and OVA-specific IgE and IgG1 levels decreased in the treatment group; however, the difference was not significant. In the cervical LNs, CD86 expression had been down-regulated in CD11c+major histocompatibility complex II-high (MHCIIhigh) in the treatment group. Additionally, IL-4 secretion in the lymphocyte culture from cervical LNs significantly decreased. CONCLUSIONS: The results confirm the antiallergic effect of intranasal 1,25-dihydroxyvitamin D3. It decreases CD 86 expression among CD11c+MHCIIhigh cells and T-helper type 2-mediated inflammation in the cervical LNs. Therefore, topically applied 1,25-dihydroxyvitamin D3 can be a future therapeutic agent for allergic rhinitis.
Administration, Intranasal ; Animals ; Anti-Allergic Agents ; Calcitriol ; Cell Proliferation ; Dendritic Cells ; Eosinophils ; Flow Cytometry ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Inflammation ; Interleukin-10 ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Lymph Nodes ; Lymphocytes ; Major Histocompatibility Complex ; Mice ; Models, Animal ; Ovalbumin ; Ovum ; Rhinitis, Allergic ; RNA, Messenger ; Vitamin D