ABSTRACT
The development of functional neurons is a complex orchestration of multiple signaling pathways controlling cell proliferation and differentiation. Because the balance of antioxidants is important for neuronal survival and development, we hypothesized that ferroptosis must be suppressed to gain neurons. We find that removal of antioxidants diminishes neuronal development and laminar organization of cortical organoids, which is fully restored when ferroptosis is inhibited by ferrostatin-1 or when neuronal differentiation occurs in the presence of vitamin A. Furthermore, iron-overload-induced developmental growth defects in C. elegans are ameliorated by vitamin E and A. We determine that all-trans retinoic acid activates the Retinoic Acid Receptor, which orchestrates the expression of anti-ferroptotic genes. In contrast, retinal and retinol show radical-trapping antioxidant activity. Together, our study reveals an unexpected function of vitamin A in coordinating the expression of essential cellular gatekeepers of ferroptosis, and demonstrates that suppression of ferroptosis by radical-trapping antioxidants or by vitamin A is required to obtain mature neurons and proper laminar organization in cortical organoids.
Subject(s)
Antioxidants , Caenorhabditis elegans , Ferroptosis , Neurons , Vitamin A , Animals , Ferroptosis/drug effects , Vitamin A/pharmacology , Vitamin A/metabolism , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/drug effects , Antioxidants/pharmacology , Neurons/metabolism , Neurons/drug effects , Neurons/cytology , Cyclohexylamines/pharmacology , Cell Differentiation/drug effects , Vitamin E/pharmacology , Receptors, Retinoic Acid/metabolism , Receptors, Retinoic Acid/genetics , Tretinoin/pharmacology , Organoids/drug effects , Organoids/metabolism , Neurogenesis/drug effects , Mice , Humans , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , Signal Transduction/drug effects , PhenylenediaminesABSTRACT
BACKGROUND: Several studies have suggested an association between vitamin deficiency and the development of tuberculosis; however, the precise impact remains unclear. This study aimed to elucidate the relationship between distinct vitamin statuses and the occurrence of tuberculosis. MATERIALS AND METHODS: Retrieval was conducted using several databases without language restrictions to capture the eligible studies on tuberculosis and vitamin status. Pooled odds ratios (ORs), relative risks (RRs), and hazard ratios (HRs) were used with 95% confidence intervals (CIs) to clarify the relationship between the different vitamin statuses (A, B, D, and E) and the occurrence of tuberculosis. Subgroup analysis, sensitivity analysis, meta-regression analysis, and Galbraith plot were performed to determine sources of heterogeneity. Potential publication biases were detected using Begg's test, Egger's test, and the trim-and-fill test. RESULTS: We identified 10,266 original records from our database searches, and 69 eligible studies were considered in this study. The random-effect model showed that people with tuberculosis may exhibit vitamin A deficiency (OR = 10.66, 95%CI: 2.61-43.63, p = .001), while limited cohort studies showed that vitamin A supplementation may reduce tuberculosis occurrence. Additionally, vitamin D deficiency was identified as a risk factor for tuberculosis development (RR = 1.69, 95%CI: 1.06-2.67, p = .026), and people with tuberculosis generally had lower vitamin D levels (OR = 2.19, 95%CI: 1.76-2.73, p < .001) compared to other groups. No publication bias was detected. CONCLUSIONS: This meta-analysis indicated that people with tuberculosis exhibited low levels of vitamins A and D, while vitamin D deficiency was identified as a risk factor for tuberculosis. More randomized controlled interventions at the community levels should be recommended to determine the association between specific vitamin supplementation and tuberculosis onset.
Subject(s)
Tuberculosis , Vitamin A Deficiency , Vitamin D Deficiency , Humans , Tuberculosis/epidemiology , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/complications , Vitamin A Deficiency/epidemiology , Vitamin A Deficiency/complications , Vitamin A Deficiency/blood , Risk Factors , Vitamin A/blood , Dietary Supplements , Vitamins/blood , Vitamin D/blood , Vitamin E Deficiency/epidemiology , Vitamin E Deficiency/complications , Vitamin E Deficiency/blood , Female , Male , Odds Ratio , Adult , Vitamin E/bloodABSTRACT
Conflicting evidence still exists regarding Vitamin B12's involvement in coronary heart disease (CHD). There is no precedent for previous studies to include both Vitamin B12, Vitamin B6, as well as Vitamin E in the consideration of CHD associating factors. Our data derived from the National Health and Nutrition Examination Survey (NHANES), which covers the period 2003-2020. 33,640 samples were included in this cross-sectional study. We used an unadjusted covariates and three adjusted covariates. The intake percentage of Vitamins E, B6, and B12 was categorized into continuous and categorical variables using multivariate logistic regression analysis and subgroup logistic regression. To estimate these trends, we applied the percentage categories of Vitamin E, B6, and B12 intake as continuous variables. We recorded Vitamin E, B6, B12, age, race, BMI, gender, household annual income, education level, hypertension status, diabetes status, smoking status, and drinking status for included samples. Multivariate regression analysis revealed that Vitamin E and B6 were negatively associated with CHD and exerted protective effects, while Vitamin B12 had little correlation with CHD. Based on the quartiles of Vitamin E and Vitamin B6 percentage, the strongest protective effect was observed in the third quartile (Q3). Analyses of subgroups showed the effects of Vitamin B6 and Vitamin E on CHD were more noticeable in women, the participant's BMI was in the 25-30 range, and participants who smoked. We identified the possible protective effect of Vitamin E and Vitamin B6 against CHD, especially in female, obese, and smoking populations, whereas income and education were also viewed as influencing factors that could be taken into account.
Subject(s)
Coronary Disease , Nutrition Surveys , Vitamin B 12 , Vitamin B 6 , Vitamin E , Humans , Female , Male , Vitamin B 12/blood , Coronary Disease/epidemiology , Middle Aged , Cross-Sectional Studies , Adult , Aged , Risk FactorsABSTRACT
OBJECTIVE: To understand the current status of protein, fat, carbohydrates, energy, vitamins, minerals and other contents in common dishes of large, small, and medium-sized restaurants in Shandong Province. METHODS: From July to October 2021, 90 Shandong cuisine dishes were collected from 9 large, medium, and small restaurants in Shandong Province. One dish was collected from each restaurant, and samples from different types of restaurants were mixed as one sample. The content of nutrients and their carbohydrate and energy levels were detected and calculated. RESULTS: The median fat and protein content detected in the 90 dishes collected were 7.7 and 6.8 g/100 g, respectively. The calculated median values of energy and carbohydrates were 528 kJ/100 g and 5.4 g/100 g, respectively. The energy supply ratio of carbohydrates per 100 g of dishes was 17.2%, fat was 55.3%, and protein was 21.4%. The content of vitamin A, vitamin B_1, vitamin B_2, vitamin C and vitamin E was trace(tr)-26 700 µg/100 g, tr-0.12 mg/100 g, tr-0.40 mg/100 g, tr-56.5 mg/100 g and tr-5.31 mg α-TE/100 g. The medium number of dishes and potassium content was 375 and 219 mg/100 g. The detection rate of trans fat acid was 81.1%, and the median content was 0.06 g/100 g. CONCLUSION: The energy supply ratio of protein and fat in dishes is relatively high, while the energy supply ratio of total carbohydrates is relatively low. The sodium content is high, showing the characteristics of high sodium and low potassium. Vitamin, especially vitamin B_1 and vitamin B_2, has a low content.
Subject(s)
Nutritive Value , Restaurants , Vitamins , China , Vitamins/analysis , Cities , Dietary Carbohydrates/analysis , Dietary Fats/analysis , Dietary Proteins/analysis , Minerals/analysis , Food Analysis , Vitamin A/analysis , Energy Intake , Vitamin E/analysis , Ascorbic Acid/analysis , Nutrients/analysis , Trace Elements/analysisABSTRACT
Prediction models were developed to assess the risk of cardiovascular disease (CVD) based on micronutrient intake, utilizing data from 90,167 UK Biobank participants. Four machine learning models were employed to predict CVD risk, with performance evaluation metrics including area under the receiver operating characteristic curve (AUC), accuracy, recall, specificity, and F1-score. The eXtreme Gradient Boosting (XGBoost) model was utilized to rank the importance of 11 micronutrients in cardiovascular health. Results indicated that vitamin E, calcium, vitamin C, and potassium intake were associated with a reduced risk of CVD. The XGBoost model demonstrated the highest performance with an AUC of 0.952, highlighting potassium, vitamin E, and vitamin C as key predictors of CVD risk. Subgroup analysis revealed a stronger correlation between calcium intake and CVD risk in older adults and those with higher BMI, while vitamin B6 intake showed a link to CVD risk in women. Overall, the XGBoost model emphasized the significance of potassium, vitamin E, and vitamin C intake as primary predictors of CVD risk in adults, with age, sex, and BMI potentially influencing the importance of micronutrient intake in predicting CVD risk.
Subject(s)
Ascorbic Acid , Cardiovascular Diseases , Vitamin E , Humans , Female , Vitamin E/administration & dosage , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Ascorbic Acid/administration & dosage , Male , Middle Aged , Adult , Potassium, Dietary/administration & dosage , Aged , Risk Assessment/methods , Machine Learning , Heart Disease Risk Factors , United Kingdom/epidemiology , Diet , Risk Factors , Body Mass IndexABSTRACT
BACKGROUND: Vitamin E ( -tocopherol) and cholesterol are crucial components in cellular protection and physiological processes. Their uses in biological media face challenges due to their poor solubility and stability. OBJECTIVE: The study investigated the complex interactions of these bioactive compounds in various encapsulation systems of cyclodextrin and liposome, as well as dispersion in PEG-6000, in an attempt to improve the viability, motility, and preservation of ovine sperm cells. MATERIALS AND METHODS: The work explored the in vitro dissolution kinetics of vitamin E (d-tocopherol) and cholesterol using semi-empirical models. RESULTS: The release profiles of VitE and Chl varied considerably, depending on the specific carrier systems. For liposome-loaded VitE and Chl, the Korsmeyer-Peppas model gave the best fit; for CD/VitE and CD/Chl, the Higuchi model provided the best fit, whereas for PEG-6000 dispersions (VitE and Chl) both the Higuchi and Korsmeyer-Peppas models demonstrated the excellent fit. All systems indicated a Fickian diffusion mechanism dictated by the concentration gradient. The delivery of VitE and Chl with CD, liposome and PEG dispersion significantly increased sperm mobility and motility. The effect on the VCL parameter was the greatest by liposome-loaded VitE and Chl, followed by CD encapsulation and PEG-6000 dispersion. CONCLUSION: The dynamics of vitamin E and cholesterol within innovative delivery systems offers valuable insights into the development of advanced solutions in reproductive health, particularly on improving the viability, motility of refrigerated ovine sperm cells. Doi.org/10.54680/fr24510110712.
Subject(s)
Cholesterol , Liposomes , Semen Preservation , Sperm Motility , Spermatozoa , Vitamin E , Animals , Male , Vitamin E/chemistry , Cholesterol/chemistry , Cholesterol/metabolism , Sheep , Semen Preservation/methods , Semen Preservation/veterinary , Spermatozoa/drug effects , Spermatozoa/physiology , Sperm Motility/drug effects , Liposomes/chemistry , Cyclodextrins/chemistry , Polyethylene Glycols/chemistry , Solubility , Cell Survival/drug effects , Cryopreservation/methodsABSTRACT
Background: In human health, vitamins play a vital role in various metabolic and regulatory processes and in the proper functioning of cells. Currently, the effect of Vitamin E (VE) intake on multiple causes of death in Chronic obstructive pulmonary disease (COPD) patients is unclear. Therefore, this paper aims to investigate the relationship between VE and multiple causes of death in COPD patients, to guide the rationalization of dietary structure and reduce the risk of COPD death. Methods: This study screened patients with COPD aged ≥40 years from the National Health and Nutrition Examination Survey (NHANES) database 2008-2018. Weighted COX regression was used to analyze the association between VE intake and multiple causes of death in COPD. The restricted cubic spline(RCS) is drawn to show their relationship. Finally, we conducted a subgroup analysis for further verification. Results: A total of 1261 participants were included in this study. After adjustment for multiple covariates, VE intake was associated with all-cause death in COPD patients, and chronic lower respiratory disease (CLRD) deaths were linearly associated with cardiovascular disease (CVD) deaths there was no such correlation. Subgroup analyses showed no interaction between subgroups, further validating the robustness of the relationship. Conclusion: In COPD patients, VE intake was negatively associated with all-cause mortality and CLRD death. Higher VE intake reduces the risk of all-cause mortality and CLRD death in COPD patients.
Subject(s)
Cause of Death , Nutrition Surveys , Pulmonary Disease, Chronic Obstructive , Vitamin E , Humans , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Disease, Chronic Obstructive/diagnosis , Male , Female , Vitamin E/administration & dosage , Middle Aged , Aged , United States/epidemiology , Risk Factors , Risk Assessment , Protective Factors , Time Factors , AdultABSTRACT
Vitamins are the essential organic substances to ensure the normal life activities of the human body. At present, vitamins are widely used in the pharmaceutical, food, animal farming, beauty and other industries, appearing in increasing application scenarios. Accordingly, the global demand for vitamins has also increased greatly. The current methods of vitamin production mainly include chemical synthesis and biosynthesis, with the latter being greener, more environmentally friendly, safer, and lower in energy consumption. Establishing the method for the biosynthesis of vitamins is of great scientific significance for achieving the goals of low carbon, energy saving, and emission reduction, as well as carbon emission peak and carbon neutrality in China. This paper reviews the research progress in the biosynthesis of vitamins, especially fat-soluble vitamins (vitamins A, D, E, and K), in recent years.
Subject(s)
Vitamin A , Vitamins , Vitamins/biosynthesis , Vitamins/metabolism , Vitamin A/metabolism , Vitamin A/biosynthesis , Vitamin E/biosynthesis , Vitamin E/metabolism , Vitamin K/metabolism , Vitamin K/biosynthesis , Vitamin D/biosynthesis , Vitamin D/metabolism , Solubility , HumansABSTRACT
Hypertrophic scarring is an aberrant wound-healing response to reestablish dermal integrity after an injury and can cause significant abnormalities in physical, aesthetic, functional, and psychological symptoms, impacting the patient's quality of life. There is currently no gold standard for preventing and treating hypertrophic scars. Therefore, many researchers have attempted to search for antihypertrophic scar agents with greater efficacy and fewer side effects. Natural therapeutics are becoming attractive as potential alternative anti-scarring agents because of their high efficacy, safety, biocompatibility, low cost, and easy accessibility. This review demonstrates various kinds of natural product-based therapeutics, including onion, vitamin E, Gotu kola, green tea, resveratrol, emodin, curcumin, and others, in terms of their mechanisms of action, evidence of efficacy and safety, advantages, and disadvantages when used as anti-scarring agents. We reviewed the literature based on data from in vitro, in vivo, and clinical trials. A total of 23 clinical trials were identified in this review; most clinical trials were ranked as having uncertain results (level of evidence 2b; n = 16). Although these natural products showed beneficial effects in both in vitro and in vivo studies of potential anti-scarring agents, there was limited clinical evidence to support their efficacy due to the limited quality of the studies, with individual flaws including small sample sizes, poor randomization, and blinding, and short follow-up durations. More robust and well-designed clinical trials with large-scale and prolonged follow-up durations are required to clarify the benefits and risks of these agents.
Subject(s)
Biological Products , Cicatrix, Hypertrophic , Humans , Cicatrix, Hypertrophic/drug therapy , Biological Products/therapeutic use , Phytotherapy , Vitamin E/therapeutic use , Curcumin/therapeutic use , Plant Extracts/therapeutic use , Onions , Wound Healing/drug effectsABSTRACT
BACKGROUND: The notable decline in the number of Tregs within Necrotizing enterocolitis (NEC) intestinal tissuesï¼contribute to excessive inflammation and necrosis, yet the precise underlying factors remain enigmatic. Ferroptosis, a novel cell death stemming from a disrupted lipid redox metabolism, is the focus of this investigation. Specifically, this study delves into the ferroptosis of Treg cells in the context of NEC and observes the protective effects exerted by vitamin E intervention, which aims to mitigate ferroptosis of Treg cells. METHODS: To investigate the reduction of Treg cells in NEC intestine, we analyzed its association with ferroptosis from multiple angles. We constructed a mouse with a specific knockout of Gpx4 in Treg cells, aiming to examine the impact of Treg cell ferroptosis on NEC intestinal injury and localized inflammation. Ultimately, we employed vitamin E treatment to mitigate ferroptosis in NEC intestine's Treg cells, monitoring the subsequent amelioration in intestinal inflammatory damage. RESULTS: The diminution of Treg cells in NEC is attributed to ferroptosis stemming from diminished GPX4 expression. Gpx4-deficient Treg cells exhibit impaired immunosuppressive function and are susceptible to ferroptosis. This ferroptosis of Treg cells exacerbates intestinal damage and inflammatory response in NEC. Notably, Vitamin E can inhibit the ferroptosis of Treg cells, subsequently alleviating intestinal damage and inflammation in NEC. Additionally, Vitamin E bolsters the anti-lipid peroxidation capability of Treg cells by upregulating the expression of GPX4. CONCLUSION: In the context of NEC, the ferroptosis of Treg cells represents a significant factor contributing to intestinal tissue damage and an exaggerated inflammatory response. GPX4 is pivotal for the viability and functionality of Treg cells. Vitamin E exhibits the capability to mitigate the ferroptosis of Treg cells, thereby enhancing their number and function, which plays a crucial role in mitigating intestinal tissue damage and inflammatory response in NEC.
Subject(s)
Enterocolitis, Necrotizing , Ferroptosis , Phospholipid Hydroperoxide Glutathione Peroxidase , T-Lymphocytes, Regulatory , Vitamin E , Animals , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Vitamin E/pharmacology , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , Mice , Enterocolitis, Necrotizing/metabolism , Enterocolitis, Necrotizing/pathology , Enterocolitis, Necrotizing/drug therapy , Disease Models, Animal , Inflammation/metabolism , Inflammation/pathology , Humans , Mice, Knockout , Intestines/pathologyABSTRACT
The aim of this work is to examine the effects of vitamin E addition to water on the structure of the gill tissue and energy metabolism of crucian carp (Carassius auratus) under cooling stress. The crucian carp were chilled using a cold acclimation intelligent chilling equipment from 20 °C to 5 °C. They were divided into three groups: the control group (E1), the negative control group (E2), and the 100 mg/L vitamin E (E3) solution. Three different temperature points (20 °C, 10 °C, and 5 °C) were used to collect, test, and analyze the samples. The findings demonstrated that in the E3 treatment group, phosphoenolpyruvate carboxykinase, acetyl coenzyme A carboxylase, total cholesterol, urea nitrogen, triglyceride, and fatty acid synthase contents were significantly lower under cooling stress than those in the E1 and E2 treatment groups (P < 0.05). The E3 therapy group had significantly greater blood glucose, glycogen, and glycogen synthase levels than the E1 and E2 treatment groups (P < 0.05). The levels of pyruvate kinase in the E1, E2, and E3 treatment groups did not differ significantly. Crucian carp's gill tissue changed under cooling stress, including capillary dilatation, and the E3 treatment group experienced less damage overall than the E1 and E2 treatment groups. In conclusion, supplementing water with vitamin E to treat crucian carp can decrease damage, improve the body's ability to withstand cold, and slow down the stress response brought on by cooling stress. This provides a theoretical basis for supplementing water with vitamin E to fish stress relief.
Subject(s)
Carps , Energy Metabolism , Gills , Vitamin E , Animals , Gills/metabolism , Gills/drug effects , Vitamin E/pharmacology , Vitamin E/metabolism , Energy Metabolism/drug effects , Carps/metabolism , Carps/physiology , Cold Temperature , Stress, Physiological/drug effects , Goldfish/metabolism , Goldfish/physiology , Glycogen/metabolism , Cold-Shock Response/drug effects , Blood Glucose/metabolismABSTRACT
Background: Chemotherapeutic drugs have some drawbacks in antineoplastic therapy, mainly containing seriously toxic side effects caused by injection and multi-drug resistance (MDR). Co-delivery with two or more drugs via nanomicelles is a promising strategy to solve these problems. Oral chemotherapy is increasingly preferred owing to its potential to enhance the life quality of patients. Methods and Results: The study intended to develop mixed micelles using D-α-Tocopherol poly(ethylene glycol) 1000 succinate (TPGS) and soluplus for the co-encapsulation of docetaxel (DTX) and curcumin (CUR), marked as (DTX+CUR)-loaded mixed micelles, treating drug-resistant breast cancer by oral administration. The (DTX+CUR)-loaded mixed micelles had a uniform particle size (~64 nm), high drug loading and encapsulation efficiency, in vitro sustained-release properties and good pH-dependent stability. In vitro cell study, the (DTX+CUR)-loaded mixed micelles displayed the highest cellular uptake, cytotoxicity, cell apoptosis-inducing rates and cell ROS-inducing levels on MCF-7/Adr cells. Notably, in vivo pharmacokinetic studies, (DTX+CUR)-loaded mixed micelles enhanced markedly the oral absorption of DTX compared to pure DTX, with a relative oral bioavailability of 574%. The (DTX+CUR)-loaded mixed micelles by oral administration had the same anticancer efficacy as taxotere by injection in resistant breast cancer bearing mice. Conclusion: (DTX+CUR)-loaded mixed micelles could provide a potential formulation for treating drug-resistant breast cancers by oral administration.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Curcumin , Docetaxel , Drug Resistance, Neoplasm , Micelles , Polyethylene Glycols , Curcumin/pharmacokinetics , Curcumin/chemistry , Curcumin/administration & dosage , Curcumin/pharmacology , Docetaxel/pharmacokinetics , Docetaxel/administration & dosage , Docetaxel/chemistry , Docetaxel/pharmacology , Humans , Female , Animals , Breast Neoplasms/drug therapy , Administration, Oral , Drug Resistance, Neoplasm/drug effects , MCF-7 Cells , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacokinetics , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Vitamin E/chemistry , Vitamin E/administration & dosage , Vitamin E/pharmacokinetics , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Polyvinyls/chemistry , Polyvinyls/pharmacokinetics , Polyvinyls/administration & dosage , Mice , Mice, Inbred BALB C , Particle Size , Taxoids/pharmacokinetics , Taxoids/administration & dosage , Taxoids/chemistry , Taxoids/pharmacology , Drug Liberation , Rats, Sprague-DawleyABSTRACT
In the pathological process of Alzheimer's disease, neuronal cell death is closely related to the accumulation of reactive oxygen species. Our previous studies have found that oxidative stress can activate microtubule affinity-regulating kinases, resulting in elevated phosphorylation levels of tau protein specifically at the Ser262 residue in N1E-115 cells that have been subjected to exposure to hydrogen peroxide. This process may be one of the pathogenic mechanisms of Alzheimer's disease. Vitamin E is a fat-soluble, naturally occurring antioxidant that plays a crucial role in biological systems. This study aimed to examine the probable processes that contribute to the inhibiting effect on the abnormal phosphorylation of tau protein and the neuroprotective activity of a particular type of vitamin E, α-tocotrienol. The experimental analysis revealed that α-tocotrienol showed significant neuroprotective effects in the N1E-115 cell line. Our data further suggest that one of the mechanisms underlying the neuroprotective effects of α-tocotrienol may be through the inhibition of microtubule affinity-regulated kinase activation, which significantly reduces the oxidative stress-induced aberrant elevation of p-Tau (Ser262) levels. These results indicate that α-tocotrienol may represent an intriguing strategy for treating or preventing Alzheimer's disease.
Subject(s)
Neurons , Neuroprotective Agents , Oxidative Stress , Vitamin E , tau Proteins , tau Proteins/metabolism , Phosphorylation/drug effects , Neurons/drug effects , Neurons/metabolism , Vitamin E/pharmacology , Vitamin E/analogs & derivatives , Neuroprotective Agents/pharmacology , Animals , Mice , Oxidative Stress/drug effects , Alzheimer Disease/metabolism , Alzheimer Disease/drug therapy , Cell Line, Tumor , TocotrienolsABSTRACT
Purpose: Ovarian cancer has the highest mortality rate and lowest survival rate among female reproductive system malignancies. There are treatment options of surgery and chemotherapy, but both are limited. In this study, we developed and evaluated micelles composed of D-α-tocopheryl polyethylene-glycol (PEG) 1000 succinate (TPGS) and Soluplus® (SOL) loaded with olaparib (OLA), a poly(ADP-ribose)polymerase (PARP) inhibitor, and rapamycin (RAPA), a mammalian target of rapamycin (mTOR) inhibitor in ovarian cancer. Methods: We prepared micelles containing different molar ratios of OLA and RAPA embedded in different weight ratios of TPGS and SOL (OLA/RAPA-TPGS/SOL) were prepared and physicochemical characterized. Furthermore, we performed in vitro cytotoxicity experiments of OLA, RAPA, and OLA/RAPA-TPGS/SOL. In vivo toxicity and antitumor efficacy assays were also performed to assess the efficacy of the mixed micellar system. Results: OLA/RAPA-TPGS/SOL containing a 4:1 TPGS:SOL weight ratio and a 2:3 OLA:RAPA molar ratio showed synergistic effects and were optimized. The drug encapsulation efficiency of this formulation was >65%, and the physicochemical properties were sustained for 180 days. Moreover, the formulation had a high cell uptake rate and significantly inhibited cell migration (**p < 0.01). In the in vivo toxicity test, no toxicity was observed, with the exception of the high dose group. Furthermore, OLA/RAPA-TPGS/SOL markedly inhibited tumor spheroid and tumor growth in vivo. Conclusion: Compared to the control, OLA/RAPA-TPGS/SOL showed significant tumor inhibition. These findings lay a foundation for the use of TPGS/SOL mixed micelles loaded with OLA and RAPA in the treatment of ovarian cancer.
Subject(s)
Micelles , Ovarian Neoplasms , Phthalazines , Piperazines , Polyethylene Glycols , Polyvinyls , Sirolimus , Vitamin E , Female , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Piperazines/chemistry , Piperazines/pharmacology , Polyethylene Glycols/chemistry , Humans , Animals , Cell Line, Tumor , Vitamin E/chemistry , Vitamin E/pharmacology , Sirolimus/chemistry , Sirolimus/pharmacology , Sirolimus/administration & dosage , Sirolimus/pharmacokinetics , Phthalazines/chemistry , Phthalazines/pharmacology , Phthalazines/administration & dosage , Phthalazines/pharmacokinetics , Polyvinyls/chemistry , Polyvinyls/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Mice , Drug Carriers/chemistry , Xenograft Model Antitumor Assays , Mice, Nude , Mice, Inbred BALB C , Cell Survival/drug effectsABSTRACT
BACKGROUND: We investigated the individual and interaction effects of maternal plasma ð- and Ï-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 ð- and Ï-tocopherol, respectively. Associations between ð-tocopherol and asthma outcome variables were inverse but not statistically significant. In contrast, for Ï-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 ð-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 ð- or Ï-tocopherol concentrations with child asthma/wheeze. We detected some evidence of effect modification by maternal asthma history in associations between ð-tocopherol and child asthma.
Subject(s)
Asthma , Prenatal Exposure Delayed Effects , Respiratory Sounds , Vitamin E , Humans , Asthma/epidemiology , Asthma/blood , Female , Pregnancy , Child , Male , Vitamin E/blood , Prenatal Exposure Delayed Effects/epidemiology , Adult , gamma-Tocopherol/blood , Cohort Studies , alpha-Tocopherol/bloodABSTRACT
This research aimed to study the long-term effects of soccer training on platelet membrane fatty acid levels and antioxidant vitamins. Forty-four subjects divided into soccer players (SP; n = 22; 20.86 ± 0.36 years) and a control group (CG; n = 22; 21.23 ± 0.49 years) participated in the study. The fatty acids of the platelet membrane, the rates of desaturation, lipid peroxidation indexes and intra-platelet levels of vitamins C and E were assessed. SP obtained lower values in polyunsaturated fatty acids 18:3:3 (alpha-linolenic acid), 20:5:3 (eicosapentaenoic acid) and 22:6:3 (docosahexaenoic acid) (p < 0.05). The desaturation index ∆5 was higher in SP (p < 0.05), and they had a higher lipid peroxidation index 20:4:6 (arachidonic acid)/16:0 (palmitic acid) (p < 0.05). Vitamin E and C platelet values were also higher in SP (p < 0.01). There were positive correlations in the ω6/ω3 index (p < 0.05), desaturation index ∆5 (p < 0.05), lipid peroxidation index 20:4:6/16:0 and intra-platelet vitamins E and C (p < 0.01) with the level of physical activity. In addition, there were inverse correlations in fatty acids 24:0 (lignoceric acid), 16:1 (palmitoleic acid), 20:3:6 (eicosadienoic acid) and 18:3:3 (alpha-linolenic acid) (p < 0.05) depending on the degree of physical activity. Regular long-term soccer training could modify the concentration of fatty acids such as 24:0, 16:1, 18:6, 20:3:6, 18:3:3:3, 20:5:3, 26:6:3 and ω3 PUFAs in the platelet membrane.
Subject(s)
Antioxidants , Blood Platelets , Lipid Peroxidation , Soccer , Humans , Blood Platelets/metabolism , Antioxidants/metabolism , Antioxidants/analysis , Soccer/physiology , Young Adult , Male , Fatty Acids/blood , Vitamin E/blood , Ascorbic Acid/blood , Cell Membrane/metabolism , Adult , Vitamins/bloodABSTRACT
Cadmium (Cd) toxicity poses a significant threat to cellular health, leading to oxidative stress and cell damage. Antioxidant agents, particularly those of natural origin, have been studied as a potential alternative for mitigating heavy metal toxicity. This study aimed to evaluate the cytoprotective effects of the antioxidant melatonin (MLT) in comparison with Vitamin E (VitE) and Trolox against Cd2+-induced cellular toxicity. The MTT assay was employed to assess cell viability in neuronal SH-SY5Y, colorectal HCT 116, and hepatic HepG2 cell lines. The results showed that all three antioxidants offered some level of protection against Cd toxicity, with Vitamin E proving to be the most effective. MLT also demonstrated a substantial cytoprotective effect, especially at the highest Cd concentration of 30 µM. These findings suggest that MLT, alongside Vit E and Trolox, could be valuable in mitigating the detrimental effects of Cd exposure by reducing the oxidative stress in these cellular models.
Subject(s)
Antioxidants , Cadmium , Cell Survival , Chromans , Melatonin , Oxidative Stress , Vitamin E , Humans , Melatonin/pharmacology , Chromans/pharmacology , Vitamin E/pharmacology , Cadmium/toxicity , Antioxidants/pharmacology , Hep G2 Cells , Oxidative Stress/drug effects , Cell Survival/drug effects , Cytoprotection/drug effects , HCT116 Cells , Cell Line, TumorABSTRACT
BACKGROUND: Childhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD. METHODS: A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored. RESULTS: APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045). CONCLUSION: The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children. TRIAL REGISTRATION: The study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023).
Subject(s)
Antioxidants , Non-alcoholic Fatty Liver Disease , Pediatric Obesity , Tocotrienols , Humans , Non-alcoholic Fatty Liver Disease/drug therapy , Male , Female , Child , Adolescent , Pediatric Obesity/complications , Pediatric Obesity/drug therapy , Tocotrienols/therapeutic use , Single-Blind Method , Antioxidants/therapeutic use , Vitamin E/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Although the relationship between oxidative stress and insulin resistance (IR) has been established, the associations of the composite dietary antioxidant index (CDAI) and its components with the surrogate index of insulin resistance (IR), triglyceride-glucose index (TyG), is still not clear. METHODS: This study analyzed the cross-sectional data of the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018. Multivariate linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were used to analyze the associations of the CDAI and its components with the TyG. In addition, subgroup analysis and several sensitivity analyses were conducted. RESULTS: A total of 14,673 participants with complete data were included, with a median age of 50 years and 7,257 women (49%). Multivariate linear regression showed that after full adjustment, the CDAI was significantly negatively associated with the TyG [ß: -0.005, 95% CI: (-0.008, -0.002), p = 0.002]. The model in which six nutrients were mutually corrected showed that vitamin E (per-SD increase) was most strongly associated with the TyG [ß: -0.062, 95% CI: (-0.074, -0.050), p < 0.0001]. In the WQS model, the WQS index of the antioxidant diet was negatively associated with the TyG (ß: -0.060; P < 0.0001). Similar effects were observed in the BKMR analysis. Notably, in the WQS and BKMR models, vitamin E became the most influential component. In addition, in the subgroup analysis, the association between the CDAI and the TyG in overweight or obese and diabetic populations was significantly weaker. CONCLUSION: Antioxidant diets, especially vitamin E, are significantly negatively correlated with TyG. This study emphasizes the important value of supplementing vitamin E to improve IR. However, patients with poor weight management and diabetes seem to benefit less from antioxidant diets.
Subject(s)
Antioxidants , Blood Glucose , Insulin Resistance , Triglycerides , Humans , Female , Antioxidants/metabolism , Middle Aged , Triglycerides/blood , Male , Cross-Sectional Studies , Blood Glucose/metabolism , Diet , Nutrition Surveys , Vitamin E/administration & dosage , Adult , Oxidative Stress/drug effects , Linear Models , Bayes TheoremABSTRACT
OBJECTIVE: Oxidative stress is strongly associated with atopic dermatitis (AD), and increased antioxidant intake could potentially reduce the risk of or alleviate its symptoms. However, the argument is disputed. Therefore, we conducted a Mendelian randomization (MR) analysis to explore the causal relationship between dietary antioxidant vitamin intake and AD. METHODS: We applied MR analysis to examine the causative association between dietary antioxidant vitamin intake (vitamin C, vitamin E, carotene, and retinol) and AD. The genome-wide association study (GWAS) summary data for antioxidant vitamins intake and AD were obtained from the IEU OpenGWAS database and the UK biobank. Our study consisted of two major parts, MR analysis to detect the causal relationship between exposure and outcome, and sensitivity analysis as supplemental evidence to verify the robustness of the results. RESULT: The results revealed a suggestive causal relationship between vitamin E intake and AD (p = 0.038, OR 95% CI = 0.745-0.992). However, there was no causal relationship between the other three vitamins (vitamin C, carotene, and retinol) and AD (p = 0.507, OR 95% CI = 0.826-1.099) (p = 0.890, OR 95% CI = 0.864-1.184) (p = 0.492, OR 95% CI = 0.893-1.264). None of the single nucleotide polymorphisms (SNPs) were detected as heterogeneous and pleiotropy in the sensitivity analysis (p > 0.05). CONCLUSION: The analysis suggested that dietary intake of vitamin E may potentially lower the risk of AD. Conversely, intake of vitamin C, retinol, and carotene is not causally related to AD. Although vitamin E intake could be protective against AD, intake of dietary antioxidant vitamins to prevent or treat AD is not necessary.