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Biological & Pharmaceutical Bulletin 2022Vitamin A is an important trace essential nutrient. Vitamin A is present as a retinyl ester in animal foods and as β-carotene (provitamin A), which is a precursor of... (Review)
Review
Vitamin A is an important trace essential nutrient. Vitamin A is present as a retinyl ester in animal foods and as β-carotene (provitamin A), which is a precursor of vitamin A, in plant foods such as green and yellow vegetables. After ingestion and absorption in the body, these are converted into retinol and stored as retinyl esters in stellate cells in the liver. The stored retinyl esters are decomposed into retinol as needed, and converted into the aldehyde retinal, which plays an important role in vision. Retinoic acid (RA) has a variety of effects. In particular, RA is used as a therapeutic agent for acute promyelocytic leukemia. This review will cover (1) elucidation of anti-refractory cancer effects of retinol (vitamin A) not mediated by RA receptors, (2) elucidation of anti-cancer effects of RA not mediated by RA receptors and (3) the development of candidate new anti-cancer agents that combine the actions of RA and retinol. Lessons learned from these findings are that vitamin A has anti-cancer activity not mediated by RA receptors; that nutritional management of vitamin A leads to prevention and treatment of cancer, and that new compounds developed from RA derivatives represent good anti-cancer drug candidates that are in various stages of clinical trials.
Topics: Animals; Antineoplastic Agents; Cell Transformation, Neoplastic; Liver; Neoplasms; Receptors, Retinoic Acid; Retinyl Esters; Tretinoin; Vitamin A
PubMed: 36047189
DOI: 10.1248/bpb.b22-00315 -
Dermatology Online Journal Oct 2022Changes to the iPLEDGE platform on December 13, 2021 made isotretinoin virtually inaccessible for many patients. Prior to the FDA approval of isotretinoin, a derivative... (Review)
Review
BACKGROUND
Changes to the iPLEDGE platform on December 13, 2021 made isotretinoin virtually inaccessible for many patients. Prior to the FDA approval of isotretinoin, a derivative of vitamin A, in 1982, vitamin A was used for severe acne.
OBJECTIVE
To review the efficacy, safety, affordability, and practicality of vitamin A as a substitute for isotretinoin when the latter is inaccessible.
METHODS
A literature review of PubMed was conducted using the key words: oral vitamin A, retinol, isotretinoin, Accutane, acne, iPLEDGE, hypervitaminosis A, and side effects.
RESULTS
We identified 9 studies (8 clinical trials and one case report); acne improved in 8 studies. Dosages ranged from 36,000IU daily to 500,000IU with 100,000IU as the most common. Mean duration until clinical improvement was 7 weeks to four months after initiation of therapy. Mucocutaneous side effects were most common, along with headaches, which resolved with either continued treatment or cessation.
CONCLUSION
Oral vitamin A is efficacious for the treatment of acne vulgaris, although the available studies have limited controls and outcomes. Side effects are qualitatively similar to those of isotretinoin and avoiding pregnancy for at least three months after stopping treatment is critical; like isotretinoin, vitamin A is a teratogen.
Topics: Humans; Isotretinoin; Vitamin A; Dermatologic Agents; Administration, Oral; Acne Vulgaris; Drug-Related Side Effects and Adverse Reactions
PubMed: 36809126
DOI: 10.5070/D328559239 -
Progress in Retinal and Eye Research Mar 2023The eye is an ideal organ for imaging by a multi-photon excitation approach, because ocular tissues such as the sclera, cornea, lens and neurosensory retina, are highly... (Review)
Review
The eye is an ideal organ for imaging by a multi-photon excitation approach, because ocular tissues such as the sclera, cornea, lens and neurosensory retina, are highly transparent to infrared (IR) light. The interface between the retina and the retinal pigment epithelium (RPE) is especially informative, because it reflects the health of the visual (retinoid) cycle and its changes in response to external stress, genetic manipulations, and drug treatments. Vitamin A-derived retinoids, like retinyl esters, are natural fluorophores that respond to multi-photon excitation with near IR light, bypassing the filter-like properties of the cornea, lens, and macular pigments. Also, during natural aging some retinoids form bisretinoids, like diretinoid-pyridiniumethanolamine (A2E), that are highly fluorescent. These bisretinoids appear to be elevated concurrently with aging. Vitamin A-derived retinoids and bisretinoidss are detected by two-photon ophthalmoscopy (2PO), using a new class of light sources with adjustable spatial, temporal, and spectral properties. Furthermore, the two-photon (2P) absorption of IR light by the visual pigments in rod and cone photoreceptors can initiate visual transduction by cis-trans isomerization of retinal, enabling parallel functional studies. Recently we overcame concerns about safety, data interpretation and complexity of the 2P-based instrumentation, the major roadblocks toward advancing this modality to the clinic. These imaging and retina-function assessment advancements have enabled us to conduct the first 2P studies with humans.
Topics: Humans; Mice; Animals; Vision, Ocular; Vitamin A; Retina; Retinoids; Retinal Pigment Epithelium
PubMed: 36787681
DOI: 10.1016/j.preteyeres.2023.101170 -
Meat Science Sep 2022To explore the effects and underlying mechanism of vitamin A on beef marbling fat development, angus steers were injected vitamin A at birth and 1 month of age and in...
To explore the effects and underlying mechanism of vitamin A on beef marbling fat development, angus steers were injected vitamin A at birth and 1 month of age and in vitro experiments were performed to investigate the effects of retinoic acid (RA) on angiogenesis and adipogenesis of intramuscular stromal vascular (SVF) cells. Results showed that vitamin A administration increased the intramuscular PDGFRα adipose progenitors, improved adipogenic potential of intramuscular SVF cells and dramatically upregulated VEGFA. At slaughter, vitamin A increased intramuscular triacylglycerols by 45% without affecting overall fatness. In a 3D culture system, RA promoted capillary sprout development and promoted the subsequent adipogenesis of intramuscular SVF cells by activating VEGFA/VEGFR2 signaling. However, during terminal adipogenesis, RA downregulated PPARγ, C/EBPα and inhibited lipid accumulation. In conclusion, vitamin A/RA upregulate VEGFA and stimulate intramuscular vascular capillary development, which increases intramuscular adipose progenitors and contributes to adipocyte formation. When administrated at neonatal stage, vitamin A promotes beef marbling development without affecting overall fatness.
Topics: Adipocytes; Adipogenesis; Adipose Tissue; Animals; Cattle; Muscle, Skeletal; Tretinoin; Vitamin A
PubMed: 35594692
DOI: 10.1016/j.meatsci.2022.108847 -
Journal of Nutritional Science 2021Countries are increasingly transitioning from event-based vitamin A supplementation (VAS) distribution to delivery through routine health system contacts, shifting also... (Review)
Review
Countries are increasingly transitioning from event-based vitamin A supplementation (VAS) distribution to delivery through routine health system contacts, shifting also to administrative, electronic-based monitoring tools, a process that brings certain limitations affecting the quality of administrative VAS coverage. At present, there is no standardised methodology for measuring the coverage of VAS delivered through routine health services. To address this gap, we conducted a systematic review of the literature to identify and recommend methods to measure VAS coverage, with the aim of providing guidance to countries on the collection of consistent data for planning, monitoring and evaluating VAS programmes integrated into routine health systems. We searched the PubMed®, Embase®, Scopus, Google Scholar and World Health Organization (WHO) Global Index Medicus databases for studies published from 1 January 2000 to 1 January 2021, reporting original data on VAS coverage and methodologies used for measurement. We screened 2371 original titles and abstracts, assessed twenty-seven full-text articles and ultimately included eighteen studies. All but two studies used a coverage cluster survey (CCS) design to measure VAS coverage, adapting the WHO Vaccination Coverage Cluster Surveys methodology, by modifying sample size and sampling parameters. Annual two-dose VAS coverage was reported from only four studies. Until electronic-based systems to collect and analyse VAS data are equipped to measure routine two-dose VAS coverage using administrative data, CCSs that comply with the 2018 WHO Vaccination Coverage Cluster Surveys Reference Manual represent the gold-standard method for effective VAS programme monitoring.
Topics: Dietary Supplements; Humans; Surveys and Questionnaires; Vitamin A; Vitamin A Deficiency
PubMed: 34527226
DOI: 10.1017/jns.2021.65 -
Gastroenterology Jul 2020
Topics: Cell Differentiation; Humans; Lymphotoxin-alpha; Tretinoin; Vitamin A; Vitamin A Deficiency
PubMed: 32413355
DOI: 10.1053/j.gastro.2020.05.029 -
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 -
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 -
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