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Biochimica Et Biophysica Acta.... Nov 2020Carotenoids are indispensable for human health, required as precursors of vitamin A and efficient antioxidants. However, these plant pigments that play a vital role in... (Review)
Review
Carotenoids are indispensable for human health, required as precursors of vitamin A and efficient antioxidants. However, these plant pigments that play a vital role in photosynthesis are represented at insufficient levels in edible parts of several crops, which creates a need for increasing their content or optimizing their composition through biofortification. In particular, vitamin A deficiency, a severe health problem affecting the lives of millions in developing countries, has triggered the development of a series of high-provitamin A crops, including Golden Rice as the best-known example. Further carotenoid-biofortified crops have been generated by using genetic engineering approaches or through classical breeding. In this review, we depict carotenoid metabolism in plants and provide an update on the development of carotenoid-biofortified plants and their potential to meet needs and expectations. Furthermore, we discuss the possibility of using natural variation for carotenoid biofortification and the potential of gene editing tools. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.
Topics: Antioxidants; Biofortification; Carotenoids; Genetic Engineering; Humans; Lipid Metabolism; Photosynthesis; Provitamins; Vitamin A
PubMed: 32068105
DOI: 10.1016/j.bbalip.2020.158664 -
Atencion Primaria 2021
Topics: Fibromyalgia; Humans; Vitamin A; Vitamin D Deficiency
PubMed: 33892225
DOI: 10.1016/j.aprim.2021.102076 -
Frontiers in Endocrinology 2023The thyroid hormones play a pivotal role in various physiological processes, including growth, metabolism regulation, and reproduction. While non-modifiable factors are... (Review)
Review
The thyroid hormones play a pivotal role in various physiological processes, including growth, metabolism regulation, and reproduction. While non-modifiable factors are known to impact thyroid function, such as genetics and age, nutritional factors are also important. Diets rich in selenium and iodine are conventionally acknowledged to be beneficial for the production and release of thyroid hormones. Recent studies have suggested a potential link between beta-carotene, a precursor to vitamin A (retinol), and thyroid function. Beta-carotene is known for its antioxidant properties and has been shown to play a role in the prevention of various clinical conditions such as cancer and cardiovascular and neurological diseases. However, its impact on thyroid function is still unclear. Some studies have suggested a positive association between beta-carotene levels and thyroid function, while others have found no significant effect. Conversely, the hormone produced by the thyroid gland, thyroxine, enhances the conversion of beta-carotene to retinol. Furthermore, vitamin A derivatives are being explored as potential therapeutic options for thyroid malignancies. In this review, we highlight the mechanisms through which beta-carotene/retinol and thyroid hormones interact and review the findings of clinical studies examining the association between beta-carotene consumption and thyroid hormone levels. Our review underscores the need for further research to clarify the relationship between beta-carotene and thyroid function.
Topics: Thyroid Gland; beta Carotene; Vitamin A; Thyroid Hormones; Physiological Phenomena
PubMed: 37305054
DOI: 10.3389/fendo.2023.1089315 -
Pflugers Archiv : European Journal of... Dec 2023Optogenetics is a technology using light-sensitive proteins to control signaling pathways and physiological processes in cells and organs and has been applied in...
Optogenetics is a technology using light-sensitive proteins to control signaling pathways and physiological processes in cells and organs and has been applied in neuroscience, cardiovascular sciences, and many other research fields. Most commonly used optogenetic actuators are sensitive to blue and green light, but red-light activation would allow better tissue penetration and less phototoxicity. Cyp27c1 is a recently deorphanized cytochrome P450 enzyme that converts vitamin A to vitamin A, thereby red-shifting the spectral sensitivity of visual pigments and enabling near-infrared vision in some aquatic species.Here, we investigated the ability of Cyp27c1-generated vitamin A to induce a shift in spectral sensitivity of the light-gated ion channel Channelrhodopsin-2 (ChR2) and its red-shifted homolog ReaChR. We used patch clamp to measure photocurrents at specific wavelengths in HEK 293 cells expressing ChR2 or ReaChR. Vitamin A incubation red-shifted the wavelength for half-maximal currents (λ) by 6.8 nm for ChR2 and 12.4 nm for ReaChR. Overexpression of Cyp27c1 in HEK 293 cells showed mitochondrial localization, and HPLC analysis showed conversion of vitamin A to vitamin A. Notably, the λ of ChR2 photocurrents was red-shifted by 10.5 nm, and normalized photocurrents at 550 nm were about twofold larger with Cyp27c1 expression. Similarly, Cyp27c1 shifted the λ of ReaChR photocurrents by 14.3 nm and increased normalized photocurrents at 650 nm almost threefold.Since vitamin A incubation is not a realistic option for in vivo applications and expression of Cyp27c1 leads to a greater red-shift in spectral sensitivity, we propose co-expression of this enzyme as a novel strategy for red-shifted optogenetics.
Topics: Humans; Vitamin A; Optogenetics; HEK293 Cells; Heart; Channelrhodopsins
PubMed: 37987804
DOI: 10.1007/s00424-023-02880-2 -
Histology and Histopathology Nov 2022Male sterility is a worldwide health problem which has troubled many unfortunate families and attracted widespread attention in the field of reproduction. Retinoic acid... (Review)
Review
Male sterility is a worldwide health problem which has troubled many unfortunate families and attracted widespread attention in the field of reproduction. Retinoic acid (RA) is a metabolite of vitamin A. Previous studies have shown that insufficient intake of vitamin A can lead to male infertility. Similarly, RA-deficiency can lead to abnormal spermatogenesis in men. RA signaling is inseparable from hormone stimulation, such as FSH, testosterone and others. It can regulate spermatogenesis as well, including the proliferation and differentiation of spermatogonia, meiosis, spermiogenesis and spermiation. To promote or inhibit spermatogenesis, RA regulates Stra8, Kit, GDNF, BMP4 and other factors in various pathways. At the self-renewal stage, RA inhibits spermatogonia renewal by directly or indirectly inhibiting DMRT, GDNF and Cyclin. At the stage of differentiation and meiosis, RA controls SSC differentiation through Kit induction and Nanos2 inhibition, and controls spermatogonia meiotic entry through up- regulation of Stra8. At the stage of spermiogenesis, RARα945;, as a key regulator, regulates spermatogenesis by up regulating Stra8 while binding with RA. Although RA plays an important role in all stages of spermatogenesis, RA signaling is more important in the early stage of spermatogonia (spg) differentiation and spermatocyte(spc) meiosis. According to the principle of RA signaling that regulates spermatogenesis, we also speculate on the future clinical application of RA, such as potential induction of SSC in vitro, contraception and restoring spermatogenesis. This paper reviews the regulatory pathways of RA, and prospects the clinical applications of RA signaling in the future.
Topics: Male; Humans; Tretinoin; Vitamin A; Signal Transduction
PubMed: 35673893
DOI: 10.14670/HH-18-478 -
Nutrients May 2022Carotenoids and vitamin A are nutrients crucial to infants’ development. To date, there is limited data on their availability in breastmilk and the associated dietary...
Carotenoids and vitamin A are nutrients crucial to infants’ development. To date, there is limited data on their availability in breastmilk and the associated dietary factors, especially in Hong Kong, where people follow a westernized Chinese diet. This study determined the selected breastmilk’s carotenoid and vitamin A (retinol) contents by ultraperformance liquid chromatography with photodiode detection (UPLC-PDA) and the dietary intakes by three-day food records in 87 Hong Kong lactating mothers, who were grouped into tertiles based on their daily carotenoid intake. Low vitamin A intake (530.2 ± 34.2 µg RAE/day) and breastmilk retinol level (1013.4 ± 36.8 nmol/L) were reported in our participants, suggesting a poor vitamin A status of the lactating participants having relatively higher socioeconomic status in Hong Kong. Mothers in the highest tertile (T3) had higher breastmilk carotenoid levels than those in the lowest (T1) (p < 0.05). There were significant associations between maternal carotenoid intakes and breastmilk lutein levels in the linear regression models (p < 0.05) regardless of dietary supplement intake. Furthermore, maternal dark green vegetable intakes were associated with breastmilk retinol, lutein, and β-carotene levels. These findings can serve as dietary references for lactating mothers to enhance breastmilk carotenoid and vitamin A contents for the benefits of child growth and development.
Topics: Carotenoids; Child; Diet; Female; Hong Kong; Humans; Infant; Lactation; Lutein; Milk, Human; Mothers; Vitamin A
PubMed: 35631170
DOI: 10.3390/nu14102031 -
International Journal of Molecular... Mar 2021Bladder cancer (BC) is the tenth most common cancer worldwide with a high recurrence rate, morbidity and mortality. Therefore, chemoprevention and improved treatment of... (Review)
Review
Bladder cancer (BC) is the tenth most common cancer worldwide with a high recurrence rate, morbidity and mortality. Therefore, chemoprevention and improved treatment of BC are of paramount importance. Epidemiological studies suggest that adequate vitamin A intake may be associated with reduced BC risk. In addition, retinoids, natural and synthetic derivatives of vitamin A, are intensively studied in cancer research due to their antioxidant properties and their ability to regulate cell growth, differentiation, and apoptosis. Findings from in vivo and in vitro models of BC show great potential for the use of retinoids in the chemoprevention and treatment of BC. However, translation to the clinical practice is limited. In this narrative review we discuss: (i) vitamin A and retinoid metabolism and retinoic acid signalling, (ii) the pathobiology of BC and the need for chemoprevention, (iii) the epidemiological evidence for the role of dietary vitamin A in BC, (iv) mechanistic insights obtained from in vivo and in vitro models, (v) clinical trials of retinoids and the limitations of retinoid use, (vi) novel systems of retinoid delivery, and (vii) components of retinoid signalling pathways as potential novel therapeutic targets.
Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents; Apoptosis; Cell Differentiation; Humans; Retinoids; Signal Transduction; Urinary Bladder Neoplasms; Vitamin A
PubMed: 33805295
DOI: 10.3390/ijms22073510 -
Molecular Metabolism Oct 2020Extrahepatic vitamin A is housed within organ-specific stellate cells that support local tissue function. These cells have been reported in the vocal fold mucosa (VFM)...
OBJECTIVE
Extrahepatic vitamin A is housed within organ-specific stellate cells that support local tissue function. These cells have been reported in the vocal fold mucosa (VFM) of the larynx; however, it is unknown how vitamin A reaches and is disseminated among VFM target cells, how VFM storage and utilization vary as a function of total body stores, and how these parameters change in the context of pathology. Therefore, in this study, we investigated fundamental VFM vitamin A uptake and metabolism.
METHODS
Using cadaveric tissue and serum from human donors representing the full continuum of clinical vitamin A status, we established a concentration range and analyzed the impact of biologic and clinical covariates on VFM vitamin A. We additionally conducted immunodetection of vitamin A-associated markers and pharmacokinetic profiling of orally dosed α-retinyl ester (a chylomicron tracer) in rats.
RESULTS
Serum vitamin A was a significant predictor of human VFM concentrations, suggesting that VFM stores may be rapidly metabolized in situ and replenished from the circulatory pool. On a vitamin A-sufficient background, dosed α-vitamin A was detected in rat VFM in both ester and alcohol forms, showing that, in addition to plasma retinol and local stellate cell stores, VFM can access and process postprandial retinyl esters from circulating chylomicra. Both α forms were rapidly depleted, confirming the high metabolic demand for vitamin A within VFM.
CONCLUSION
This thorough physiological analysis validates VFM as an extrahepatic vitamin A repository and characterizes its unique uptake, storage, and utilization phenotype.
Topics: Aged; Aged, 80 and over; Animals; Female; Hepatic Stellate Cells; Humans; Liver; Male; Middle Aged; Mucous Membrane; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Vitamin A; Vocal Cords
PubMed: 32473404
DOI: 10.1016/j.molmet.2020.101025 -
Leukemia Aug 2023Vitamin C has been demonstrated to regulate hematopoietic stem cell frequencies and leukemogenesis by augmenting and restoring Ten-Eleven Translocation-2 (TET2)...
Vitamin C has been demonstrated to regulate hematopoietic stem cell frequencies and leukemogenesis by augmenting and restoring Ten-Eleven Translocation-2 (TET2) function, potentially acting as a promising adjunctive therapeutic agent for leukemia. However, glucose transporter 3 (GLUT3) deficiency in acute myeloid leukemia (AML) impedes vitamin C uptake and abolishes the clinical benefit of vitamin C. In this study, we aimed to investigate the therapeutic value of GLUT3 restoration in AML. In vitro GLUT3 restoration was conducted with the transduction of GLUT3-overexpressing lentivirus or the pharmacological salvage with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) treatment to OCI-AML3, a naturally GLUT3-deficient AML cell line. The effects of GLUT3 salvage were further confirmed in patient-derived primary AML cells. Upregulation of GLUT3 expression made AML cells successfully augment TET2 activity and enhanced the vitamin C-induced anti-leukemic effect. Pharmacological GLUT3 salvage has the potential to overcome GLUT3 deficiency in AML and improves the antileukemic effect of vitamin C treatments.
Topics: Humans; Ascorbic Acid; Glucose Transporter Type 3; Leukemia, Myeloid, Acute; Vitamin A; Translocation, Genetic; DNA-Binding Proteins; Dioxygenases
PubMed: 37393342
DOI: 10.1038/s41375-023-01954-5 -
Pediatrics Jan 2021Evidence suggests that intramuscular vitamin A reduces the risk of bronchopulmonary dysplasia (BPD) in preterm infants. Our objective was to compare enteral... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Evidence suggests that intramuscular vitamin A reduces the risk of bronchopulmonary dysplasia (BPD) in preterm infants. Our objective was to compare enteral water-soluble vitamin A with placebo supplementation to reduce the severity of BPD in extremely preterm infants.
METHODS
We conducted a double-blind randomized controlled trial in infants <28 weeks' gestation who were to receive either enteral water-soluble vitamin A (5000 IU per day) or a placebo. Supplementation was started within 24 hours of introduction of feeds and continued until 34 weeks' postmenstrual age (PMA). The primary outcome was the severity of BPD, assessed by using the right shift of the pulse oximeter saturation versus the inspired oxygen pressure curve.
RESULTS
A total of 188 infants were randomly assigned. The mean ± SD birth weight (852 ± 201 vs 852 ± 211 g) and gestation (25.8 ± 1.49 vs 26.0 ± 1.39 weeks) were comparable between the vitamin A and placebo groups. There was no difference in the right shift (median [25th-75th percentiles]) of the pulse oximeter saturation versus inspired oxygen pressure curve (in kilopascals) between the vitamin A (11.1 [9.5-13.7]) and placebo groups (10.7 [9.5-13.1]) ( = .73). Enteral vitamin A did not affect diagnosis of BPD or other clinical outcomes. Plasma retinol levels were significantly higher in the vitamin A group versus the placebo group on day 28 and at 34 weeks' PMA.
CONCLUSIONS
Enteral water-soluble vitamin A supplementation improves plasma retinol levels in extremely preterm infants but does not reduce the severity of BPD.
Topics: Administration, Oral; Bronchopulmonary Dysplasia; Double-Blind Method; Female; Humans; Infant, Extremely Premature; Infant, Newborn; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Prospective Studies; Severity of Illness Index; Treatment Outcome; Vitamin A; Vitamins
PubMed: 33386338
DOI: 10.1542/peds.2020-009985