The effects of TGF-ß-induced activation and starvation of vitamin A and palmitic acid on human stem cell-derived hepatic stellate cells.

BACKGROUND: Hepatic stellate cells (HSC) have numerous critical roles in liver function and homeostasis, while they are also known for their importance during liver injury and fibrosis. There is therefore a need for relevant in vitro human HSC models to fill current knowledge gaps. In particular, the roles of vitamin A (VA), lipid droplets (LDs), and energy metabolism in human HSC activation are poorly understood. METHODS: In this study, human pluripotent stem cell-derived HSCs (scHSCs), benchmarked to human primary HSC, were exposed to 48-hour starvation of retinol (ROL) and palmitic acid (PA) in the presence or absence of the potent HSC activator TGF-ß. The interventions were studied by an extensive set of phenotypic and functional analyses, including transcriptomic analysis, measurement of activation-related proteins and cytokines, VA- and LD storage, and cell energy metabolism. RESULTS: The results show that though the starvation of ROL and PA alone did not induce scHSC activation, the starvation amplified the TGF-ß-induced activation-related transcriptome. However, TGF-ß-induced activation alone did not lead to a reduction in VA or LD stores. Additionally, reduced glycolysis and increased mitochondrial fission were observed in response to TGF-ß. CONCLUSIONS: scHSCs are robust models for activation studies. The loss of VA and LDs is not sufficient for scHSC activation in vitro, but may amplify the TGF-ß-induced activation response. Collectively, our work provides an extensive framework for studying human HSCs in healthy and diseased conditions.

Vitamin D Maintains Growth and Bone Mineral Density against a Background of Severe Vitamin A Deficiency and Moderate Toxicity in a Swine Model.

Excessive vitamin A (VA) negatively impacts bone. Interactions between VA and vitamin D (VD) in bone health are not well-understood. This study used a traditional two-by-two factorial design. Pigs were weaned and randomized to four treatments (n = 13/group): -A-D, -A+D, +A-D, and +A+D for 3 and 5 wk. Serum, liver, kidney, adrenal glands, spleen, and lung were analyzed by ultra-performance LC. Growth was evaluated by weight measured weekly and BMD by DXA. Weights were higher in -A+D (18.1 ± 1.0 kg) and +A+D (18.2 ± 2.3 kg) at 5 wk than in -A-D (15.5 ± 2.1 kg) and +A-D (15.8 ± 1.5 kg). Serum retinol concentrations were 0.25 ± 0.023, 0.22 ± 0.10, 0.77 ± 0.12, and 0.84 ± 0.28 µmol/L; and liver VA concentrations were 0.016 ± 0.015, 0.0065 ± 0.0035, 2.97 ± 0.43, 3.05 ± 0.68 µmol/g in -A-D, -A+D, +A-D, and +A+D, respectively. Serum 25(OH)D3 concentrations were 1.5 ± 1.11, 1.8 ± 0.43, 27.7 ± 8.91, and 23.9 ± 6.67 ng/mL in -A-D, +A-D, -A+D, +A+D, respectively, indicating a deficiency in -D and adequacy in +D. BMD was highest in +D (p < 0.001). VA and the interaction had no effect on BMD. Dietary VD influenced weight gain, BMD, and health despite VA status.

Maternal vitamin A and D status in second and third trimester of pregnancy and bone mineral content in offspring at nine years of age.

Introduction: Maternal nutritional and vitamin status during pregnancy may have long-term effects on offspring health and disease. The aim of this study was to examine the associations between maternal vitamin A and D status in pregnancy and offspring bone mineral content (BMC) at nine years of age. Methods: This is a post-hoc study of a randomized control trial including 855 pregnant women from two Norwegian cities; Trondheim and Stavanger. The women were randomized into an exercise intervention or standard antenatal care. Mother and child pairs for the present study were recruited from those still living in Trondheim after 8-10 years. Serum vitamin A (retinol) and vitamin D (25(OH)D) were measured in the 2nd and 3rd trimesters of pregnancy, and active vitamin D (1,25(OH)2D) in serum was measured in a subgroup. Spine BMC and trabecular bone score were measured in the children at nine years of age. Associations were analyzed with linear regression models. Results: A total of 119 mother and child pairs were included in the analyses. Vitamin A insufficiency (retinol< 1.05 µmol/L) and vitamin D deficiency (25(OH)D< 50 mmol/L) increased from ~7% to ~43% and from ~28% to ~33%, respectively, from the 2nd to the 3rd trimester. An increase in serum 1,25(OH)2D from the 2nd to the 3rd trimester was observed in the subgroup. There was a negative association between serum retinol in the 2nd trimester and spine BMC in the boys, but not in the girls, when adjusted for maternal and child confounders. No other associations between maternal serum vitamin A or D and BMC in the children were found. Conclusion: We observed a high prevalence of vitamin A insufficiency and vitamin D deficiency during pregnancy. A negative association between mid-pregnancy vitamin A status and spine BMC was observed in boys, but not girls, while no associations were found between maternal vitamin D status and child BMC. The implications of optimal vitamin A and D status in pregnancy for offspring bone health, remains a subject for further investigations.

The potential contributions of bouillon fortification to meeting micronutrient requirements among women and preschool children in Senegal: A modeling study using household consumption and expenditure survey data.

To reduce micronutrient deficiencies, Senegal mandates the fortification of refined oil with vitamin A and wheat flour with iron and folic acid. Expanding Senegal's large-scale food fortification programs to include fortified bouillon could help fill the remaining gaps in dietary micronutrient requirements. Using 7-day household food consumption data collected between 2018 and 2019, we assessed the potential contributions of bouillon fortified with vitamin A (40-250 µg/g bouillon), folic acid (20-120 µg/g), vitamin B12 (0.2-2 µg/g), iron (0.6-5 mg/g), and zinc (0.6-5 mg/g) for meeting micronutrient requirements of women of reproductive age (WRA; 15-49 years old) and children (6-59 months old). Most households (90%) reported consuming bouillon, including poor and rural households. At modeled fortification levels, bouillon fortification reduced the national prevalence of inadequacy by up to ∼20 percentage points (pp) for vitamin A, 34 pp (WRA) and 20 pp (children) for folate, 20 pp for vitamin B12, 38 pp (WRA) and 30 pp (children) for zinc, and ∼8 pp for iron. Predicted reductions in inadequacy were generally larger among poor and rural populations, especially for vitamins A and B12. Our modeling suggests that bouillon fortification has the potential to substantially reduce dietary inadequacy of multiple micronutrients and could also help address inequities in dietary micronutrient inadequacies in Senegal.

The First Steps of the Visual Cycle in Human Rod and Cone Photoreceptors.

Purpose: Light detection destroys the visual pigment. Its regeneration, necessary for the recovery of light sensitivity, is accomplished through the visual cycle. Release of all-trans retinal by the light-activated visual pigment and its reduction to all-trans retinol comprise the first steps of the visual cycle. In this study, we determined the kinetics of all-trans retinol formation in human rod and cone photoreceptors. Methods: Single living rod and cone photoreceptors were isolated from the retinas of human cadaver eyes (ages 21 to 90 years). Formation of all-trans retinol was measured by imaging its outer segment fluorescence (excitation, 360 nm; emission, >420 nm). The extent of conversion of released all-trans retinal to all-trans retinol was determined by measuring the fluorescence excited by 340 and 380 nm. Measurements were repeated with photoreceptors isolated from Macaca fascicularis retinas. Experiments were carried out at 37°C. Results: We found that ∼80% to 90% of all-trans retinal released by the light-activated pigment is converted to all-trans retinol, with a rate constant of 0.24 to 0.55 min-1 in human rods and ∼1.8 min-1 in human cones. In M. fascicularis rods and cones, the rate constants were 0.38 ± 0.08 min-1 and 4.0 ± 1.1 min-1, respectively. These kinetics are several times faster than those measured in other vertebrates. Interphotoreceptor retinoid-binding protein facilitated the removal of all-trans retinol from human rods. Conclusions: The first steps of the visual cycle in human photoreceptors are several times faster than in other vertebrates and in line with the rapid recovery of light sensitivity exhibited by the human visual system.

Endoplasmic reticulum stress as a target for retinoids in cancer treatment.

Retinoids, natural and synthetic derivatives of vitamin A, have various regulatory activities including controlling cellular proliferation, differentiation, and death. Furthermore, they have been used to treat specific cancers with satisfying results. Nevertheless, retinoids have yet to be converted into effective systemic therapies for the majority of tumor types. Regulation of unfolded protein response signaling, and persistent activation of endoplasmic reticulum stress (ER-stress) are promising treatment methods for cancer. The present article reviews the current understanding of how vitamin A and its derivatives may aid to cause ER-stress-activated apoptosis, as well as therapeutic options for exploiting ER-stress for achieving beneficial goal. The therapeutic use of some retinoids discussed in this article was related to decreased disease recurrence and improved therapeutic outcomes via ER-stress activation and promotion, indicating that retinoids may play an important role in cancer treatment and prevention. More research is needed to expand the use of vitamin A derivatives in cancer therapy, either alone or in combination with unfolded protein response inducers.

Vitamin A influences the incretin hormone profiles by activating the retinoic acid receptor ß.

BACKGROUND: This study aimed to investigate the impact of Vitamin A (VA) on intestinal glucose metabolic phenotypes. METHODS: Male C57BL/6 mice were randomized assigned to a VA-normal diet (VAN) or a VA-deficient diet (VAD) for 12 weeks. After12 weeks, the VAD mice were given 30 IU/g/d retinol for 10 days and VAN diet (VADN) for 10 weeks. By using glucose tolerance tests, immunofluorescence staining, quantitative polymerase chain reaction, siRNA transduction, and enzyme-linked immunosorbent assay, the glucose metabolic phenotypes as well as secretory function and intracellular hormone changes of STC-1 were assessed. RESULTS: VAD mice showed a decrease of glucose-stimulated insulin secretion and a loss of intestinal glucagon-like peptide-1 (GLP-1) expression. Through reintroducing dietary VA to VAD mice, the intestinal VA levels, GLP-1 expression and normal glucose can be restored. The incubation with retinol increased VA signaling factors expression within STC-1 cells, especially retinoic acid receptor ß (RARß). The activation of RARß restored intracellular incretin hormone synthesis and secretory function. CONCLUSIONS: VA deficiency leads to an imbalance of intestinal glucose metabolic phenotypes through a mechanism involving RARß signaling pathway, suggesting a new method to achieve the treatment for VAD induced glucose metabolism impairment.

Effects of supplementation of grazing Nellore cows with ß-carotene and vitamins A + D3 + E + biotin on follicle diameter, oestrus, establishment of pregnancy, and foetal morphometry.

The objectives of this experiment were to evaluate the effects of supplementation of Nellore (Bos indicus) cows with ß-carotene + vitamins A + D3 + E + biotin on body condition score (BCS), oestrus, pregnancy, and foetal morphometry. Lactating cows (n = 497) from two herds were balanced for BCS and calving period [early calving (EC); late calving (LC)] and were assigned randomly to: Control (n = 251)-supplementation with a mineral supplement; and SUP (n = 246)-supplementation with the mineral supplement fed to control + ß-carotene (150 mg/day) + vitamin A (40,000 IU/day) + vitamin D3 (5000 IU/day) + vitamin E (300 mg/day) + biotin (20 mg/day). Cows were supplemented from Days -30 to 30 (Day 0 = timed artificial insemination; TAI). Pregnancy was diagnosed 30 days after TAI and foetal crown-rump distance and thoracic diameter were measured at 30 and 77 days of gestation. Cows in the SUP treatment were more likely to have BCS ≥3.0 on Day 0 (63.0 ± 3.1 vs. 60.2 ± 3.1; p < .01) and were more likely to gain BCS from Days -30 to 30 (57.7 ± 3.3 vs. 44.1 ± 3.3%; p < .01). Fewer LC cows in the SUP treatment were detected in oestrus at the time of the first TAI (Control: LC: 75.4 ± 4.4 vs. SUP: LC: 64.0 ± 5.2 vs. Control: EC: 65.3 ± 4.0 vs. SUP: EC: 71.8 ± 3.7; p = .04). There was a tendency for the SUP treatment to increase pregnancy to the first TAI (64.2 ± 3.0 vs. 56.6 ± 3.1%; p = .08). A greater percentage of SUP cows was detected in oestrus at the time of the second TAI (70.1 ± 5.0 vs. 52.3 ± 4.8%; p = .01). The SUP treatment increased pregnancy to the second TAI among LC cows (SUP: LC: 75.9 ± 8.0% vs. Control: LC: 50.0 ± 8.3% vs. Control: EC: 52.0 ± 5.9% vs. SUP: EC: 41.4 ± 6.5%; p = .02). The SUP treatment increased foetal size (crown-rump; p = .04 and thoracic diameter; p < .01) at 30 days of gestation and, despite decreasing crow-rump length at 77 days after the first TAI among EC cows (p < .01), it increased the thoracic diameter at 77 days after the first TAI independent of calving season. Our results support that pregnancy establishment and foetal growth can be improved when grazing Nellore cows are supplemented with ß-carotene and vitamins A + D3 + E + biotin.

Early childhood height is a determinant of young adult stature in rural Nepal.

BACKGROUND: Does preschool height predict adult stature in undernourished settings? The extent to which preschool length or height forecasts young adult stature is unclear in chronically undernourished populations. METHODS: In 2006-8, we assessed height in a cohort of 2074 young adults, aged 16-23 years, in rural Nepal who, as preschoolers (≤ 4 year), were measured at baseline and again 16 months later during a vitamin A supplementation trial in 1989-91. We assessed by linear regression the ability of preschool length (L, measured < 24 mo) or height (Ht, 24-59 mo), at each year of age to predict 16-23 year old height, adjusted for month of young adult age, interval duration (in months), caste, preschool weight-for-height z-score and, in young women, time since menarche, marriage status and pregnancy history. RESULTS: Young women were a mean of 0.81, 1.11, 0.82, 0.24, 0.44 cm taller (all p < 0.01) and young men, 0.84, 1.18, 0.74, 0.64 and 0.48 cm taller (all p < 0.001) per cm of attained L/Ht at each successive preschool year of age and, overall, were 2.04 and 2.40 cm taller for each unit increase in preschool L/Ht z-score (L/HAZ) (both p < 0.001). Coefficients were generally larger for 16-month follow-up measurements. The percent of young adult height attained by children with normal L/HAZ (>-1) increased from 38-40% mid-infancy to ∼ 69-74% by 6 years of age. By 3-6 years of age heights of stunted children (L/HAZ<-2) were consistently ∼ 4-7% lower in their young adult height versus normal statured children. There was no effect of preschool vitamin A receipt. CONCLUSIONS: Shorter young children become shorter adults but predictive effects can vary by sex, age assessed, and may be influenced by year or season of measurement.

Multilayered collagen-lipid hybrid nanovesicles for retinol stabilization and efficient skin delivery.

Lipid-based nanocarriers have been extensively utilized for the solubilization and cutaneous delivery of water-insoluble active ingredients in skincare formulations. However, their practical application is often limited by structural instability, leading to premature release and degradation of actives. Here we present highly robust multilamellar nanovesicles, prepared by the polyionic self-assembly of unilamellar vesicles with hydrolyzed collagen peptides, to stabilize all-trans-retinol and enhance its cutaneous delivery. Our results reveal that the reinforced multilayer structure substantially enhances dispersion stability under extremely harsh conditions, like freeze-thaw cycles, and stabilizes the encapsulated retinol. Interestingly, these multilamellar vesicles exhibit significantly lower cytotoxicity to human dermal fibroblasts than their unilamellar counterparts, likely due to their smaller particle number per weight, minimizing potential disruptions to cellular membranes. In artificial skin models, retinol-loaded multilamellar vesicles effectively upregulate collagen-related gene expression while suppressing the synthesis of metalloproteinases. These findings suggest that the robust multilamellar vesicles can serve as effective nanocarriers for the efficient delivery and stabilization of bioactive compounds in cutaneous applications.

Association between dietary vitamin A intake and risk of cardiometabolic multimorbidity.

The association between vitamin A and single cardiometabolic diseases has been extensively studied, but the relationship between dietary vitamin A intake and the risk of cardiometabolic multimorbidity (CMM) has not been studied. Therefore, the present study was conducted to explore the association with CMM risk by analyzing different sources of vitamin A. This study utilized 13,603 subjects aged ≥ 18 years from 1997 to 2015 from the China Health and Nutrition Survey (CHNS). Dietary intake was calculated from 3 consecutive 24-h dietary recalls combined with a house hold food inventory. CMM is defined as the development of at least two cardiometabolic diseases. After a median follow-up of 9.0 years, there were 1050 new cases of CMM. The risk of CMM was significantly lower in those with higher vitamin A intake (Q1 vs Q5 HR 0.66, 95% CI 0.54-0.81). ß-carotene (Q1 vs Q5 HR 0.82, 95% CI 0.66-1.02) and retinol (Q1 vs Q5 HR 0.59, 95% CI 0.48-0.73) intake had a similarly negative correlation. Using restricted cubic spline found an L-shaped relationship between retinol intake and CMM (p non-linear < 0.001). Negative associations were also found in specific CMD groups (hypertension, cardiovascular disease, stroke and diabetes). Dietary intake of vitamin A was negatively associated with CMM risk, and this protective effect was more pronounced in patients with cardiovascular disease. There was an L-shaped association between retinol intake and CMM risk.

The combination of tetramethylpyrazine and vitamin A acid in the treatment of skin photoaging by activating the HIF-1α pathway.

Skin photoaging is a skin degenerative disease that causes patients to develop malignant tumors. The existing clinical treatment of photoaging has limitations. This greatly reduces the recovery rate of photoaging patients. Studies have confirmed that Ligusticum wallichii Franch (LWF) monomer tetramethylpyrazine (TMP) alleviates various skin diseases. The combination of traditional Chinese medicine and Western medicine helps with this process. Our research aimed to explore the specific treatment mode and molecular mechanism of TMP in treating skin photoaging. CCK-8 assays were used to evaluate the activity and toxicity of HaCaT cells. ß-galactosidase aging, Carbonyl compound and nitrosylated tyrosine assays were used to analyze the aging of HaCaT cells. ROS assays and ELISA were used to analyze the enrichment of ROS. The molecular docking experiment analyzed the binding of TMP and HIF-1α. qRT-PCR and Western blot were used to detect the activation of skin aging-related pathways. HE staining was used to analyze the thickness of the stratum corneum skin on the back skin of mice. 200µg/L LWF alleviates cellular photoaging and mouse skin photoaging by reducing ROS enrichment. Its monomer TMP plays an important role in this process. The combination of TMP and HIF-1α accelerates the degradation of ROS by activating the Nrf2/ARE signaling pathway. This process reduces the apoptosis of cells damaged by light. In addition, we also found that the combination of TMP and retinoic acid (RA) is more beneficial for the treatment of skin damage caused by light in mice. The combination therapy of TMP and RA alleviates skin oxidative stress response through overexpression of HIF-1α. This plan is beneficial for the treatment of skin photoaging.

Calculation of reference intervals for the concentrations of α-tocopherol and retinol in serum using indirect data-mining procedures.

BACKGROUND: Establishing adequate reference intervals (RIs) for vitamins A and E is essential for diagnosing and preventing deficiencies. Due to the current boom in data mining and its easy applicability, more laboratories are establishing RIs using indirect methods. Our study aims to obtain RIs using four indirect data-mining procedures (Bhattacharya, Hoffmann, Kosmic, and RefineR) for vitamins A and E. MATERIAL AND METHODS: 8943 individuals were collected to establish the RIs. After using different data cleaning steps and checking whether these data should be divided according to age and gender based on multiple linear regression and variance component analyses, indirect RIs were calculated using specific Excel spreadsheets or R-packages software. RESULTS: A total of 2004 records were eligible. For vitamin A, the RIs obtained were (1.11 - 2.68) µmol/L, (1.13 - 2.70) µmol/L, (1.13 - 2.71) µmol/L, and (1.17 - 2.66) µmol/L using the Bhattacharya, Hoffmann, Kosmic and RefineR approaches, respectively. For vitamin E, these intervals were (17.3 - 49.9) µmol/L (Bhattacharya), (17.3 - 48.9) µmol/L (Hoffmann), (19.6 - 50.3) µmol/L (Kosmic), and (19.4 - 50.9) µmol/L (RefineR). In all cases, the RIs were comparable. CONCLUSIONS: Suitable RIs for vitamins A and E were calculated using four indirect methods that are suitable and adapted to our population's demographic characteristics.

Modeled impacts of bouillon fortification with micronutrients on child mortality in Senegal, Burkina Faso, and Nigeria.

Micronutrient interventions can reduce child mortality. By applying Micronutrient Intervention Modeling methods in Senegal, Burkina Faso, and Nigeria, we estimated the impacts of bouillon fortification on apparent dietary adequacy of vitamin A and zinc among children and folate among women. We then used the Lives Saved Tool to predict the impacts of bouillon fortification with ranges of vitamin A, zinc, and folic acid concentrations on lives saved among children 6-59 months of age. Fortification at 250 µg vitamin A/g and 120 µg folic acid/g was predicted to substantially reduce vitamin A- and folate-attributable deaths: 65% for vitamin A and 92% for folate (Senegal), 36% for vitamin A and 74% for folate (Burkina Faso), and >95% for both (Nigeria). Zinc fortification at 5 mg/g would avert 48% (Senegal), 31% (Burkina Faso), and 63% (Nigeria) of zinc-attributable deaths. The addition of all three nutrients at 30% of Codex nutrient reference values in 2.5 g bouillon was predicted to save an annual average of 293 child lives in Senegal (3.5% of deaths from all causes among children 6-59 months of age), 933 (2.1%) in Burkina Faso, and 18,362 (3.7%) in Nigeria. These results, along with evidence on program feasibility and costs, can help inform fortification program design discussions.

Establishment of Reference Range for Serum Concentration of Vitamin A and Vitamin E in Southern Sichuan Area of China.

OBJECTIVE: To establish the reference range of serum concentration of vitamin A (VA) and vitamin E (VE) in Southern Sichuan area of China. METHODS: From August 1, 2021, to May 31, 2023, 9482 blood tablets were received for the screening of VA and VE. The information was divided into four different age groups: ≤1 year old, 1< to ≤6 years, 6< to ≤17 years, and 17< to ≤59 years. In each age group, the four seasons were further subdivided into spring, summer, autumn, and winter, as well as male and female genders. The serum concentration of VA and VE was detected by liquid chromatography-tandem mass spectrometry (HPLC-MS), and the reference range was established for verification. RESULTS: The concentration of VA and VE in 9482 cases showed skewed distribution. When comparing between different age groups, the serum concentration of VA and VE was statistically significant (p < 0.05). While comparing different seasons, the serum VA levels in different seasons were significantly different (p < 0.05) except in summer and autumn. There was statistical significance in VE level in different seasons (p < 0.05). And while comparing different genders, there was no statistical significance in VA concentration levels (p > 0.05). The VE concentration levels were statistically significant (p < 0.05). The established reference range was established and verified, and the results were in accordance with the standard. CONCLUSION: The reference range of VA and VE should be set according to different ages, different seasons, and different genders.

Effects of long-term intake of carotenoid-enriched eggs on healthy people: a randomized controlled study.

Red palm oil, a natural repository abundant in tocotrienols, tocopherols and carotenoids, is frequently employed as a pigment and nutritional enhancer in food products. The principal aim of this study is to explore the disparities in vitamin A levels, fatty acid profiles and gut microbiota among healthy adults who consume carotenoid-enriched eggs compared to those who consume normal eggs. A total of 200 hens were randomly assigned to either the red palm oil group or the soybean oil group, with the objective of producing carotenoid-enriched eggs and normal eggs. Throughout a six-month, double-blinded, randomized controlled trial, participants were instructed to consume one carotenoid-enriched or normal egg daily at a fixed time. Fecal and blood samples were collected from the participants at the start and conclusion of the six-month intervention period for further analysis. Our findings indicated that there was no significant change in the vitamin A level for daily supplementation with one carotenoid-enriched egg, but there were significant changes in some indicators of fatty acid profiles and gut microbiota compared to the control group of the population. Nonetheless, the consumption of eggs, regardless of carotenoid-enriched eggs or normal eggs, positively influenced dietary habits by reducing the intake of saturated fatty acids and enhancing the intake of monounsaturated and polyunsaturated fatty acids of the population.

Association of Dietary Retinol Intake and Serum Neurofilament Light Chain Levels: Results from NHANES 2013-2014.

BACKGROUND: There is increasing evidence suggesting that serum neurofilament light chain (sNfL) levels can be used as biomarkers for axonal injury. Retinol is recognized for its significant involvement in nervous system function, but the precise connection between dietary retinol and sNfL levels remains uncertain. OBJECTIVE: Our objective was to investigate the relationship between dietary retinol intake and sNfL, and to find an optimal retinol intake level for neurological health. METHODS: In the National Health and Nutrition Examination Survey (NHANES), conducted from 2013 to 2014, a cohort of 1684 participants who met the criteria were selected for the study. sNfL levels were measured from stored serum samples using a novel high-throughput immunoassay platform from Siemens Healthineers. Assessment of dietary retinol intake was performed by a uniformly trained interviewer through a 24 h dietary recall method. A generalized linear model was evaluated to assess the correlation between dietary retinol intake and sNfL concentrations. Furthermore, the nonlinear association between the two is further explored using restricted cubic spline (RCS) analysis. RESULTS: Upon adjusting for potential confounders, a 10% increase in dietary retinol intake was associated with a 3.47% increase in sNfL levels (95% CI: 0.54%, 6.49%) across all participants. This relationship was more pronounced in specific subgroups, including those under 60 years of age, non-obese, impaired estimated glomerular filtration rate (eGFR), and non-diabetic. In subgroup analysis, among those younger than 60 years of age (percent change: 3.80%; 95% CI: 0.43%, 7.28%), changes were found in non-obese participants (percent change: 6.28%; 95% CI: 2.66%, 10.02%), those with impaired eGFR (percent change: 6.90%; 95% CI: 1.44%, 12.65%), and non-diabetic patients (percentage change: 4.17%; 95% CI: 1.08%, 7.36%). RCS analysis showed a linear relationship between dietary retinol intake and sNfL levels. Furthermore, the positive correlation between the two was more significant after the inflection point, according to piecewise linear analysis. CONCLUSION: This current investigation uncovered a J-shaped relationship between dietary retinol and sNfL levels, suggesting that axonal damage can occur when dietary retinol intake increases more than a specific threshold. These findings need to be further confirmed in future prospective studies to determine the precise intake level that may trigger axonal injury.

Dissecting the binding effect of Crocetin glucosyltransferase 2 in crocetin biotransformation in saffron (Crocus sativus L.) from different origins.

Crocus sativus L. is a both medicinal and food bulbous flower whose qualities are geographically characterized. However, identification involving different places of origin of such substances is currently limited to single-omics mediated content analysis. Integrated metabolomics and proteomics, 840 saffron samples from six countries (Spain, Greece, Iran, China, Japan, and India) were analyzed using the QuEChERS extraction method. A total of 77 differential metabolites and 14 differential proteins were identified. The limits of detection of the method were 1.33 to 8.33 µg kg-1, and the recoveries were 85.56% to 105.18%. Using homology modeling and molecular docking, the Gln84, Lys195, Val182 and Pro184 sites of Crocetin glucosyltransferase 2 were found to be the targets of crocetin binding. By multivariate statistical analysis (PCA and PLS-DA), different saffron samples were clearly distinguished. The results provided the basis for the selection and identification of high quality saffron from different producing areas.

The DNA methylation status of the vitamin A signaling associated with testicular degeneration induced by long-day photoperiods in Magang geese.

Magang geese are typical short-day breeders whose reproductive behaviors are significantly influenced by photoperiod. Exposure to a long-day photoperiod results in testicular regression and spermatogenesis arrest in Magang geese. To investigate the epigenetic influence of DNA methylation on the seasonal testicular regression in Magang geese, we conducted whole-genome bisulfite sequencing and transcriptome sequencing of testes across 3 reproductive phases during a long-day photoperiod. A total of 250,326 differentially methylated regions (DMR) were identified among the 3 comparison groups, with a significant number showing hypermethylation, especially in intronic regions of the genome. Integrating bisulfite sequencing with transcriptome sequencing data revealed that DMR-associated genes tend to be differentially expressed in the testes, highlighting a potential regulatory role for DNA methylation in gene expression. Furthermore, there was a significant negative correlation between changes in the methylation of CG DMRs and changes in the expression of their associated genes in the testes. A total of 3,359 DMR-associated differentially expressed genes (DEG) were identified; functional enrichment analyses revealed that motor proteins, MAPK signaling pathway, ECM-receptor interaction, phagosome, TGF-beta signaling pathway, and calcium signaling might contribute to the testicular regression process. GSEA revealed that the significantly enriched activated hallmark gene set was associated with apoptosis and estrogen response during testicular regression, while the repressed hallmark gene set was involved in spermatogenesis. Our study also revealed that methylation changes significantly impacted the expression level of vitamin A metabolism-related genes during testicular degeneration, with hypermethylation of STRA6 and increased calmodulin levels indicating vitamin A efflux during the testicular regression. These findings were corroborated by pyrosequencing and real-time qPCR, which revealed that the vitamin A metabolic pathway plays a pivotal role in testicular degeneration under long-day conditions. Additionally, metabolomics analysis revealed an insufficiency of vitamin A and an abnormally high level of oxysterols accumulated in the testes during testicular regression. In conclusion, our study demonstrated that testicular degeneration in Magang geese induced by a long-day photoperiod is linked to vitamin A homeostasis disruption, which manifests as the hypermethylation status of STRA6, vitamin A efflux, and a high level of oxysterol accumulation. These findings offer new insights into the effects of DNA methylation on the seasonal testicular regression that occurs during long-day photoperiods in Magang geese.

Faecal microbiota of schoolchildren is associated with nutritional status and markers of inflammation: a double-blinded cluster-randomized controlled trial using multi-micronutrient fortified rice.

Faecal microbiota plays a critical role in human health, but its relationship with nutritional status among schoolchildren remains under-explored. Here, in a double-blinded cluster-randomized controlled trial on 380 Cambodian schoolchildren, we characterize the impact of six months consumption of two types of rice fortified with different levels of vitamins and minerals on pre-specified outcomes. We investigate the association between the faecal microbiota (16SrRNA sequencing) and age, sex, nutritional status (underweight, stunting), micronutrient status (iron, zinc and vitamin A deficiencies, anaemia, iron deficient anaemia, hemoglobinopathy), inflammation (systemic, gut), and parasitic infection. We show that the faecal microbiota is characterised by a surprisingly high proportion of Lactobacillaceae. We discover that deficiencies in specific micronutrients, such as iron and vitamin A, correlate with particular microbiota profiles, whereas zinc deficiency shows no such association. The nutritional intervention with the two rice treatments impacts both the composition and functions predicted from compositional analysis in different ways. (ClinicalTrials.gov (Identifier: NCT01706419)).