The presence of free palmitic acid modulates the effects of lutein on structural and dynamic properties of lipid membranes.

Free fatty acids, like palmitic acid (PA), and xanthophyll pigments, like lutein (LUT) are the natural membrane compounds in plants. To study the effect of PA on LUT and their organization, a model membrane of 1,2-dimyristoyl-sn-glycerol-3-phosphocholine (DMPC) enriched with 2 mol% PA and 1 mol% LUT was formed. Molecular mechanisms underlying the interaction between these two compounds were examined with application of molecular spectroscopy techniques, e.g., visible spectroscopy, electron paramagnetic resonance and Fourier transform infrared. We determined the monomeric/dimeric organization of LUT in the membrane. We proved that the presence of PA in the lipid phase facilitated and stabilized the formation of LUT structures in the membrane. Lutein with PA did not form strong molecular aggregates like H- and J-structures. We presented the simplified model membrane that could be a suitable representation of the physiological process of de-esterification of PA from LUT appearing in natural biomembranes in humans.

A robust multinutrient kinetic model for enhanced lutein and biomass yields in mixotrophic microalgae cultivation: A step towards successful large-scale productions.

Mixotrophic cultivation holds great promise to significantly enhance the productivities of biomass and valuable metabolites from microalgae. In this study, a new kinetic model is developed, explicitly describing the effect of the most influential environmental factors on both biomass growth and the production of the high-value product lutein. This extensive study of multinutrient kinetics for Tetradesmus obliquus in a mixotrophic regime covers various nutritional conditions. Crucial nutrients governing the model include nitrate, phosphate, and glucose. Using seven state variables and 13 unknown parameters, the model's accuracy was ensured through a well-designed two-factor, four-level experimental setup, providing ample data for reliable calibration and validation. Results accurately predict dynamic concentration profiles for all validation experiments, revealing broad applicability. Optimizing nitrogen availability led to significant increases in biomass (up to fourfold) and lutein production (up to 12-fold), with observed maximum biomass concentration of 6.80 g L-1 and lutein reaching 25.58 mg L-1. Noticeably, the model exhibits a maximum specific growth rate of 4.03 day-1, surpassing reported values for photoautotrophic and heterotrophic conditions, suggesting synergistic effects. Valuable guidance is provided for applying the method to various microalgal species and results are large-scale production-ready. Future work will exploit these results to develop real-time photobioreactor operation strategies.

Lutein supplementation for early-life health and development: current knowledge, challenges, and implications.

Macular carotenoids, which consist of lutein, zeaxanthin, and meso-zeaxanthin, are dietary antioxidants and macular pigments in the eyes, protecting the macula from light-induced oxidative stress. Lutein is also the main carotenoid in the infant brain and is involved in cognitive development. While a few articles reviewed the role of lutein in early health and development, the current review is the first that focuses on the outcomes of lutein supplementation, either provided to mothers or to infants. Additionally, lutein status and metabolism during pregnancy and lactation, factors that limit the potential application of lutein as a nutritional intervention, and solutions to overcome the limitation are also discussed. In brief, the lutein intake in pregnant and lactating women in the United States may not be optimal. Furthermore, preterm and formula-fed infants are known to have compromised lutein status compared to term and breast-fed infants, respectively. While lutein supplementation via both maternal and infant consumption improves lutein status in infants, the application of lutein as a nutritional intervention may be compromised by its low bioavailability. Various encapsulation techniques have been developed to enhance the delivery of lutein in adult animals or human but should be further evaluated in neonatal models.

Longitudinal analysis of carotenoid content in preterm human milk.

To describe the variability in carotenoid content of human milk (HM) in mothers of very to extremely low birth weight preterm infants throughout lactation and to explore the relationship between lutein in HM and the occurrence of retinopathy of prematurity (ROP) in preterm infants. We recruited healthy mothers along with their preterm infants that were born at gestational age 24 + 2 to 29 + 6 weeks or with a birth weight under 1500 g and were exclusively breastfed HM. Each participant provided up to 7 HM samples (2-10 ml) on day 0-3 and once a week until 6 weeks. Additionally, when possible, a blood sample was collected from the infant at week 6. Concentrations of the major carotenoids (lutein, zeaxanthin, beta-carotene, and lycopene) in all HM and blood samples were assessed and compared. Thirty-nine mother-infant dyads were included and 184 HM samples and 21 plasma samples were provided. Mean lutein, zeaxanthin, beta-carotene, and lycopene concentration decreased as lactation progressed, being at their highest in colostrum samples (156.9 vs. 66.9 vs. 363.9 vs. 426.8 ng/ml, respectively). Lycopene (41%) and beta-carotene (36%) were the predominant carotenoids in colostrum and up to 2 weeks post-delivery. Inversely, the proportion of lutein and zeaxanthin increased with lactation duration to account for 45% of the carotenoids in mature HM. Lutein accounted for 58% of the carotenoids in infant plasma and only 28% in HM. Lutein content of transition and mature HM did not differ between mothers of ROP and non-ROP infants.Conclusion Carotenoid content of HM was dynamic and varied between mothers and as lactation progressed. Infant plasma displayed a distinct distribution of carotenoids from HM.

Current understanding and future directions of cruciferous vegetables and their phytochemicals to combat neurological diseases.

Neurological disorders incidences are increasing drastically due to complex pathophysiology, and the nonavailability of disease-modifying agents. Several attempts have been made to identify new potential chemicals to combat these neurological abnormalities. At present, complete abolishment of neurological diseases is not attainable except for symptomatic relief. However, dietary recommendations to help brain development or improvement have increased over the years. In recent times, cruciferous vegetables and their phytochemicals have been identified from preclinical and clinical investigations as potential neuroprotective agents. The present review highlights the beneficial effects and molecular mechanisms of phytochemicals such as indole-3-carbinol, diindolylmethane, sulforaphane, kaempferol, selenium, lutein, zeaxanthin, and vitamins of cruciferous vegetables against neurological diseases including Parkinson's disease, Alzheimer's disease, stroke, Huntington's disease, autism spectra disorders, anxiety, depression, and pain. Most of these cruciferous phytochemicals protect the brain by eliciting antioxidant, anti-inflammatory, and antiapoptotic properties. Regular dietary intake of cruciferous vegetables may benefit the prevention and treatment of neurological diseases. The present review suggests that there is a lacuna in identifying the clinical efficacy of these phytochemicals. Therefore, high-quality future studies should firmly establish the efficacy of the above-mentioned cruciferous phytochemicals in clinical settings.

A mechanistic review on growing multiple therapeutic applications of lutein and its global market research.

Lutein is a naturally occurring carotenoid synthesized by plants and algae that has a beneficial effect on several biological processes and associated ailments. Its immediate application is in ophthalmology, where it significantly lowers the incidences of age-related macular degeneration (AMD). It also has anti-inflammatory action, treatment of diabetic retinopathy, and cataracts, and enhancement of visual contrast. To critically assess lutein biosynthesis, therapeutic applicability, and market research literature. We have discussed its theoretical frameworks, experimental evidence, limitations, as well as clinical trial results, and future research prospects. The literature for this review article was mined and compiled by collecting and analyzing articles from several databases, including ScienceDirect, Google Scholar, PubMed, Wiley Online Library, Patentscope, and ClinicalTrials.gov published until March 30, 2022. Patent publications were identified using the search terms like IC:(C07C67/56) AND EN_AB:(lutein) OR EN_TI:(lutein) OR EN_AB:(extraction) OR EN_TI:(process). According to the literature, lutein is an essential nutrient given that it cannot be synthesized in the human body and acts as an antioxidant, affecting AMD, diabetic retinopathy, Rheumatic diseases, inflammation, and cancer. Due to inadequate production and laborious extraction, lutein is expensive despite its high demand and applicability. Market research predicts a 6.3% compound annual growth rate for lutein by 2032. Optimizing lutein extraction for high yield and purity is necessary. Lutein has proven applicability in various ailments as well as cosmetics that can be developed as a candidate drug for various diseases discussed in the review.

Bone morphogenetic protein 6 induces downregulation of pentraxin 3 expression in human granulosa lutein cells in women with polycystic ovary syndrome.

PURPOSE: To evaluate whether PTX3 is differentially expressed in the granulosa lutein cells derived from women with PCOS and whether BMP6 can regulate the expression of PTX3 in hGL cells. METHODS: The expression levels of BMP6 and PTX3 in granulosa lutein cells were evaluated by RT-qPCR. The correlation between the expression levels of BMP6 /PTX3 and oocyte quality indexes were analyzed using clinical samples. The cells were incubated with BMP6 at different concentrations and times to check the expression of PTX3 in KGN cells. TGF-ß type I inhibitors and small interfering RNA targeting ALK2/3/6,SMAD1/5/8 and SMAD4 were used to study the involvement of SMAD dependent pathways in KGN cells. RESULTS: The levels of BMP6 in hGL cells were negatively correlated with the corresponding oocyte maturation rate and high-quality embryo rate, whereas the levels of PTX3 were positively correlated with the corresponding oocyte maturation rate in PCOS. Additionally, the in vitro cell cultured results showed BMP6 significantly inhibited the expression of PTX3 in KGN cells. Furthermore, using a dual inhibition approach (kinase inhibitors and small interfering RNAs), we identified the ALK2/ALK3 type I receptors and BMPR2/ACVR2A type II receptors and the downstream SMAD1/SMAD5-SMAD4 signaling pathway were responsible for the BMP6-induced cellular activities in KGN cells. CONCLUSIONS: The suppressive effect of BMP6 on PTX3 was mediated by ALK2/ALK3 type I receptors and BMPR2/ACVR2A type II receptors in granulosa cells through the SMAD1/5-SMAD4 dependent signaling pathway in PCOS.Our findings provides new insights into the understanding of the pathogenesis of PCOS-related ovulatory disorders.

Lutein Production and Extraction from Microalgae: Recent Insights and Bioactive Potential.

Microalgae have been reported to be excellent producers of bioactive molecules. Lutein is a pigment reported to have various beneficial effects for humans, and especially for eye well-being. In the current review, we summarize various methods that have been developed to optimize its extraction and bioactivities reported for human health. Several protective effects have been reported for lutein, including antioxidant, anticancer, anti-inflammatory, and cardioprotective activity. This review also reports attempts to increase lutein production by microalgae by changing culturing parameters or by using pilot-scale systems. Genetic engineering lutein production is also discussed. Considering the increasing aging of the worldwide population will create an increased need for lutein, a viable economic and eco-sustainable method to produce lutein is needed to face this market demand.

Selective Removal of Chlorophyll and Isolation of Lutein from Plant Extracts Using Magnetic Solid Phase Extraction with Iron Oxide Nanoparticles.

In recent years, there has been a growing interest in plant pigments as readily available nutraceuticals. Photosynthetic pigments, specifically chlorophylls and carotenoids, renowned for their non-toxic antioxidant properties, are increasingly finding applications beyond their health-promoting attributes. Consequently, there is an ongoing need for cost-effective methods of isolation. This study employs a co-precipitation method to synthesize magnetic iron oxide nanoparticles. Scanning electron microscopy (SEM) coupled with energy dispersive spectrometry (EDS) confirms that an aqueous environment and oxidizing conditions yield nanosized iron oxide with particle sizes ranging from 80 to 140 nm. X-ray photoelectron spectroscopy (XPS) spectra indicate the presence of hydrous iron oxide FeO(OH) on the surface of the nanosized iron oxide. The Brunauer-Emmett-Teller (BET) surface area of obtained nanomaterial was 151.4 m2 g-1, with total pore volumes of pores 0.25 cm3 g-1 STP. The material, designated as iron oxide nanoparticles (IONPs), serves as an adsorbent for magnetic solid phase extraction (MSPE) and isolation of photosynthetic pigments (chlorophyll a, lutein) from extracts of higher green plants (Mentha piperita L., Urtica dioica L.). Sorption of chlorophyll a onto the nanoparticles is confirmed using UV-vis spectroscopy, Fourier transform infrared photoacoustic spectroscopy (FT-IR/PAS), and high-performance liquid chromatography (HPLC). Selective sorption of chlorophyll a requires a minimum of 3 g of IONPs per 12 mg of chlorophyll a, with acetone as the solvent, and is dependent on a storage time of 48 h. Extended contact time of IONPs with the acetone extract, i.e., 72 h, ensures the elimination of remaining components except lutein, with a spectral purity of 98%, recovered with over 90% efficiency. The mechanism of chlorophyll removal using IONPs relies on the interaction of the pigment's carbonyl (C=O) groups with the adsorbent surface hydroxyl (-OH) groups. Based on molecular dynamics (MD) simulations, it has been proven that the selective adsorption of pigments is also influenced by more favorable dispersion interactions between acetone and chlorophyll in comparison with other solutes. An aqueous environment significantly promotes the removal of pigments; however, it results in a complete loss of selectivity.

Comprehensive Analysis of Lutein and Loroxanthin in Scenedesmus obliquus: From Quantification to Isolation.

Carotenoids are hydrophobic pigments produced exclusively by plants, fungi, and specific microbes. Microalgae are well suited for the production of valuable carotenoids due to their rapid growth, efficient isoprenoid production pathway, and ability to store these compounds within their cells. The possible markets for bio-products range from feed additives in aquaculture and agriculture to pharmaceutical uses. The production of carotenoids in microalgae is affected by several environmental conditions, which can be utilized to enhance productivity. The current study focused on optimizing the extraction parameters (time, temperature, and extraction number) to maximize the yield of carotenoids. Additionally, the impact of various nitrogen sources (ammonia, nitrate, nitrite, and urea) on the production of lutein and loroxanthin in Scenedesmus obliquus was examined. To isolate the carotenoids, 0.20 g of biomass was added to 0.20 g of CaCO3 and 10.0 mL of ethanol solution containing 0.01% (w/v) pyrogallol. Subsequently, the extraction was performed using an ultrasonic bath for a duration of 10 min at a temperature of 30 °C. This was followed by a four-hour saponification process using a 10% methanolic KOH solution. The concentration of lutein and loroxanthin was measured using HPLC-DAD at 446 nm, with a flow rate of 1.0 mL/min using a Waters YMC C30 Carotenoid column (4.6 × 250 mm, 5 µm). The confirmation of carotenoids after their isolation using preparative chromatography was achieved using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with an atmospheric pressure chemical ionization (APCI) probe and UV-vis spectroscopy. In summary, S. obliquus shows significant promise for the large-scale extraction of lutein and loroxanthin. The findings of this study provide strong support for the application of this technology to other species.

Simultaneous Intake of Chlorella and Ascidian Ethanolamine Plasmalogen Accelerates Activation of BDNF-TrkB-CREB Signaling in Rats.

Brain-derived neurotrophic factor (BDNF) plays an important role in neurogenesis, synaptic plasticity, and cognition. BDNF is a neurotrophin that binds to tropomyosin receptor kinase B (TrkB), a specific receptor on target cell surfaces; it acts on neuronal formation, development, growth, and repair via transcription factors, such as cAMP response element-binding protein (CREB), and it is involved in learning and memory. BDNF expression is decreased in patients with Alzheimer's disease (AD). Exercise and the intake of several different foods or ingredients can increase BDNF expression, as confirmed with lutein, xanthophylls (polar carotenoids), and ethanolamine plasmalogen (PlsEtn), which are present at high levels in the brain. This study examined the effects of combining lutein and PlsEtn using lutein-rich Chlorella and ascidian extracts containing high levels of PlsEtn bearing docosahexaenoic acid, which is abundant in the human brain, on the activation of the BDNF-TrkB-CREB signaling pathway in the hippocampus of Sprague-Dawley rats. Although activation of the BDNF-TrkB-CREB signaling pathway in the hippocampus was not observed in Chlorella or ascidian PlsEtn monotherapy, activation was observed with combination therapy at an equal dose. The results of this study suggest that the combination of Chlorella and ascidian PlsEtn may have a preventive effect against dementia, including AD.

Lutein Loaded in ß-Cyclodextrin Metal-Organic Frameworks for Stability and Solubility Enhancements.

Lutein (Lut) is a recognized nutritional supplement known for its antioxidative and anti-inflammatory properties, crucial in mitigating ocular disease. However, enhancements to Lut stability and solubility remain challenges to be addressed in the healthcare industry. Herein, we fabricated and evaluated a food-grade highly porous ß-cyclodextrin metal-organic framework (ß-CD-MOF) for its ability to encapsulate Lut. Lut stability considerably improved when loaded into ß-CD-MOF to form a Lut@ß-CD-MOF complex, which exhibited better stability than Lut loaded into the γ-cyclodextrin metal-organic framework (Lut@γ-CD-MOF), Lut@ß-CD, and commercial product (Blackmores™) at 40°C, 60°C, and 70°C, respectively. The solubility of Lut@ß-CD-MOF in water increased by 26.8-fold compared to raw Lut at 37°C. Lut@ß-CD-MOF exhibited greater hydrophilicity, as determined by measuring the water contact angle. Molecular docking and other characterizations of Fourier transform infrared spectroscopy and powder X-ray diffraction confirmed that Lut was successfully encapsulated in the chamber formed by the three cyclodextrins in ß-CD-MOF. Thermogravimetric analysis and Raman spectroscopy demonstrated that Lut distributed in the ß-CD-MOF cavity deeply improved Lut stability and solubility. In conclusion, our findings underscored the function of ß-CD-MOF in enhancing Lut stability and solubility for formulation applications.

Microbial chassis as the platform for production of dihydroxy xanthophyll-based carotenoids: an overview of recent advances in biomanufacturing.

Physiological and environmental cues prompt microbes to synthesize diverse carotenoids, including dihydroxy xanthophylls, facilitating their adaptation and survival. Lutein and its isomeric counterpart, zeaxanthin, are notable dihydroxy xanthophylls with bioactive properties such as antioxidative, anti-inflammatory, anticancer, and neuroprotective effects, particularly beneficial for human ocular health. However, global natural resources for co-producing lutein and zeaxanthin are scarce, with zeaxanthin lacking commercial sources, unlike lutein sourced from marigold plants and microalgae. Traditionally, dihydroxy xanthophyll production primarily relies on petrochemical synthetic routes, with limited biological sourcing reported. Nonetheless, microbiological synthesis presents promising avenues as a commercial source, albeit challenged by low dihydroxy xanthophyll yield at high cell density. Strategies involving optimization of physical and chemical parameters are essential to achieve high-quality dihydroxy xanthophyll products. This overview briefly discusses dihydroxy xanthophyll biosynthesis and highlights recent advancements, discoveries, and industrial benefits of lutein and zeaxanthin production from microorganisms as alternative biofactories.

Changes in the Expression Profile of Pyroptosis-Related Genes in Senescent Retinal Pigment Epithelial Cells after Lutein Treatment.

Retinal pigment epithelium (RPE) is a specialized structure essential for proper vision, which is constantly exposed to oxidative damage. With aging, this damage accumulates within the RPE cells, causing various diseases, including age-related macular degeneration (AMD). Numerous antioxidant substances are used to prevent this process in humans, including lutein. This study aims to determine the differences in the expression patterns of pyroptosis genes in senescent human retinal pigment epithelial cell line ARPE-19 exposed to lutein. Changes in the expression of pyroptosis-related genes were assessed by oligonucleotide microarrays, and the results were validated by real-time RT-qPCR. The microarray analysis showed seven transcripts were differentially expressed both in the H2O2-treated cells versus the controls and in the lutein/H2O2-treated cells compared to the H2O2-treated cells (FC > 2.0). Depending on the used lutein, H2O2, or co-treatment of ARPE-19 cells, statistically significant differences in the expression of TXNIP, CXCL8, BAX, and CASP1 genes were confirmed by the RT-qPCR (p < 0.05). A STRING database analysis showed that the proteins encoded by the analyzed genes form a strong interaction network (p < 0.001). These data indicate that lutein modulates the expression level of pyroptosis-related genes, which may be useful for the development of new methods preventing pyroptosis pathway activation in the future.

Macular Pigment Optical Density and Skin Carotenoids in a Childhood Sample.

BACKGROUND: Carotenoids are plant pigments with light filtering and antioxidant properties that deposit in human tissues, including retina and skin. Descriptive characteristics and covariates of carotenoid status in macula and skin have been examined in adults; however, similar studies in children are limited. Thus, this study aimed to delineate how factors of age, sex, race, weight status, and dietary carotenoid intake relate to macular and skin carotenoids in children. METHODS: Children (7-13 y, N = 375) completed heterochromatic flicker photometry to assess macular pigment optical density (MPOD). Participants underwent anthropometrics to measure weight status (BMI percentile [BMI%]), and parent/guardian provided demographic information. Subsample data were available for skin carotenoids (N = 181), assessed using reflection spectroscopy, and dietary carotenoids (N = 101) using the Block Food Frequency Questionnaire. Relationships between skin and macular carotenoids were assessed using partial Pearson's correlations controlling for age, sex, race, and BMI%. Relationships between dietary carotenoids and macular and skin carotenoids were assessed using stepwise linear regression including age, sex, race, and BMI% in the model. RESULTS: Mean MPOD was 0.56 ± 0.22 and skin carotenoid score was 282 ± 94.6. There was no significant correlation between MPOD and skin carotenoids (r = 0.02, P = 0.76). BMI% was negatively associated with skin (stdß = -0.42, P < 0.001), but not macular carotenoids (stdß = -0.04, P = 0.70). Neither MPOD nor skin carotenoids were associated with age, sex, or race (all P > 0.10). MPOD was positively associated with energy-adjusted reported lutein + zeaxanthin intake (stdß = 0.27, P = 0.01). Skin carotenoids were positively associated with energy-adjusted reported carotenoid intake (stdß = 0.26, P = 0.01). CONCLUSIONS: The mean MPOD values in children were higher than what has been reported in adult populations. Previous studies in adult samples report an average MPOD of 0.21. Although macular and skin carotenoids were not related, they were associated with dietary carotenoids relevant to the respective tissues; however, skin carotenoids may be more susceptible negative influence from higher weight status.

Randomized, Placebo-Controlled, Single-Blind Study of Lutein Supplementation on Carotenoid Status and Cognition in Persons with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is traditionally managed using disease-modifying pharmaceutical therapies as a first line approach for treatment, yet there is increasing interest in lifestyle factors, particularly diet, for managing disease outcomes. Lutein has neuroprotective properties in healthy adults, but no previous research has examined the effects of lutein supplementation in persons with MS. OBJECTIVES: This study aimed to investigate the efficacy of 4-mo lutein supplementation on carotenoid status and cognition in persons with relapse-remitting MS (RRMS). METHODS: A randomized controlled, single-blind research design was used among adults with RRMS (N = 21). Participants were randomized into placebo (n = 9) or treatment (20-mg/d lutein, n = 12) groups with outcomes measured before and after 4 mo. Macular pigment optical density (MPOD) was assessed using heterochromatic flicker photometry. Skin carotenoids were assessed using reflection spectroscopy. Serum lutein was measured using high-performance liquid chromatography. Cognition was assessed via the Eriksen flanker with event-related potentials, spatial reconstruction, and the symbol digit modalities tests. RESULTS: There was a significant group by time interaction for MPOD (F = 6.74, P = 0.02), skin carotenoids (F = 17.30, P < 0.01), and serum lutein (F = 24.10, P < 0.01), whereby the treatment group improved in all carotenoid outcomes. There were no significant group by time interactions for cognitive and neuroelectric outcomes. However, increase in MPOD was positively associated with accuracy during the flanker incongruent trials (r = 0.55, P = 0.03) and the spatial memory task (r = 0.58, P = 0.02) among treatment participants. CONCLUSIONS: Lutein supplementation increases carotenoid status among persons with RRMS. There is no significant effect on cognitive function but change in macular carotenoids is selectively associated with improved attention and memory. This study provides preliminary support for a fully powered study targeting retinal and neural carotenoids for cognitive benefits in persons with MS. This trial was registered at clinicaltrials.gov as NCT04843813.

Systemic Effects of Prenatal Carotenoid Supplementation in the Mother and her Child: The Lutein and Zeaxanthin in Pregnancy (L-ZIP) Randomized Trial -Report Number 1.

BACKGROUND: Adding carotenoids, particularly lutein (L) and zeaxanthin (Z), to prenatal micronutrient formulations has been promoted to enhance infant visual and neural development and to maintain maternal health. Although these claims are biologically plausible, they are not yet supported by a compelling prospective trial. OBJECTIVE: We investigated the effect of prenatal carotenoid supplementation on biomarkers of maternal and infant systemic carotenoid status. METHODS: We randomly assigned 47 first trimester pregnant subjects by 1:1 allocation to receive standard-of-care prenatal vitamins plus a 10 mg L and 2 mg Z softgel (the Carotenoid group) or standard-of-care prenatal vitamins with a placebo softgel (the Control group) for 6-8 mo. Maternal carotenoid concentrations in the serum and skin at the end of each trimester and postpartum were measured with HPLC and resonance Raman spectroscopy, respectively. Infants' systemic carotenoid status was assessed using similar techniques but optimized for infants. Repeated measures and paired t-tests were determined, and a P value < 0.05 was considered statistically significant. RESULTS: After supplementation, there was a statistically significant increase in maternal serum L + Z concentrations, serum total carotenoid concentrations, and skin carotenoid status (P < 0.001 for all) in the Carotenoid group relative to the Control group at all study time points. Similarly, infants whose mothers were in the Carotenoid group had a significant 5-fold increase in cord blood L + Z concentrations, over a 3-fold increase in cord blood total carotenoids, and a 38% increase in skin carotenoids compared with the Control group (P < 0.0001 for all). In addition, there was a strong positive, statistically significant correlation between postpartum maternal and infant systemic carotenoid status (P < 0.0001). CONCLUSION: Prenatal carotenoid supplementation significantly increased maternal and infant systemic (skin and serum) carotenoid status, which may benefit pregnant women and their infants' health. This trial was registered at clinicaltrials.gov as NCT03750968.

Lutein targeting orbital fibroblasts attenuates fibrotic and inflammatory effects in thyroid-associated ophthalmopathy.

Lutein (LU) is a carotenoid that has recently been implicated in multiple roles in fibrosis, inflammation, and oxidative stress. Thyroid-associated ophthalmopathy (TAO) is particularly relevant to these pathological changes. We thus aim to probe the potential therapeutic effects of TAO in an in vitro model. We used LU pre-treating OFs derived from patients with TAO or not, then treated with TGF-ß1(or IL-1ß)to induce fibrosis (or inflammation). We analyzed the different expressions of related genes and proteins, and the molecular mechanism pathway on TAO OFs was screened by RNA sequencing, which is identified in vitro. We found that LU attenuates fibrotic and inflammatory effects in TAO. LU inhibited ACTA2, COL1A1, FN1, and CTGF mRNA expression and suppressed α-SMA, and FN1 protein expression induced by TGF-ß1. Besides, LU suppressed OFs migration. Besides, it is shown that LU suppressed inflammation-related genes, such as IL-6, IL-8, CXCL1, and MCP-1. Moreover, LU inhibited oxidative stress induced by IL-1ß, which is analyzed by DHE fluorescent probe staining. RNA sequencing suggested ERK/AP-1 pathway may be the molecular mechanism of LU protective effect on TAO, which is identified by RT-qPCR and western-blot. In summary, this study provides the first evidence that LU significantly attenuates the pathogenic manifestations of TAO by inhibiting the expression of fibrotic and inflammation-related genes and ROS produced by OFs. These data suggested that LU may be a potential medicine for TAO.

Mechanism for the selective uptake of macular carotenoids mediated by the HDL cholesterol receptor SR-BI.

The macular carotenoids lutein and zeaxanthin are taken up from the bloodstream into the human retina through a selective process, for which the HDL cholesterol receptor scavenger receptor BI (SR-BI) in the cells of retinal pigment epithelium (RPE) is thought to be a key mediator. However, the mechanism of SR-BI-mediated selective uptake of macular carotenoids is still not fully understood. Here, we investigate possible mechanisms using biological assays and cultured HEK293 cells, a cell line without endogenous SR-BI expression. Binding affinities between SR-BI and various carotenoids were measured by surface plasmon resonance (SPR) spectroscopy, which shows that SR-BI cannot bind lutein or zeaxanthin specifically. Overexpression of SR-BI in HEK293 cells results in more lutein and zeaxanthin taken up than ß-carotene, and this effect can be eliminated by an SR-BI mutant (C384Y) whose cholesterol uptake tunnel is blocked. Next, we determined the effects of HDL and hepatic lipase (LIPC), SR-BI's partners in HDL cholesterol transport, on SR-BI-mediated carotenoid uptake. HDL addition dramatically reduced lutein, zeaxanthin, and ß-carotene in HEK293 cells expressing SR-BI, but the cellular lutein and zeaxanthin are higher than ß-carotene. LIPC addition increases the uptake of all three carotenoids in HDL-treated cells, and promotes the transport of lutein and zeaxanthin better than ß-carotene. Our results suggest that SR-BI and its HDL cholesterol partner HDL and LIPC may be involved in the selective uptake of macular carotenoids.

Hierarchical dynamic regulation of Saccharomyces cerevisiae for enhanced lutein biosynthesis.

Lutein, as a carotenoid with strong antioxidant capacity and an important component of macular pigment in the retina, has wide applications in pharmaceutical, food, feed, and cosmetics industries. Besides extraction from plant and algae, microbial fermentation using engineered cell factories to produce lutein has emerged as a promising route. However, intra-pathway competition between the lycopene cyclases and the conflict between cell growth and production are two major challenges. In our previous study, de novo synthesis of lutein had been achieved in Saccharomyces cerevisiae by dividing the pathway into two stages (δ-carotene formation and conversion) using temperature as the input signal to realize sequential cyclation of lycopene. However, lutein production was limited to microgram level, which is still too low to meet industrial demand. In this study, a dual-signal hierarchical dynamic regulation system was developed and applied to divide lutein biosynthesis into three stages in response to glucose concentration and culture temperature. By placing the genes involved in δ-carotene formation under the glucose-responsive ADH2 promoter and genes involved in the conversion of δ-carotene to lutein under temperature-responsive GAL promoters, the growth-production conflict and intra-pathway competition were simultaneously resolved. Meanwhile, the rate-limiting lycopene ε-cyclation and carotene hydroxylation reactions were improved by screening for lycopene ε-cyclase with higher activity and fine tuning of the P450 enzymes and their redox partners. Finally, a lutein titer of 19.92 mg/L (4.53 mg/g DCW) was obtained in shake-flask cultures using the engineered yeast strain YLutein-3S-6, which is the highest lutein titer ever reported in heterologous production systems.