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Nutrients Jun 2023Dysregulation of lipid metabolism has been implicated in age-related macular degeneration (AMD), the leading cause of blindness among the elderly. Lecithin cholesterol...
Dysregulation of lipid metabolism has been implicated in age-related macular degeneration (AMD), the leading cause of blindness among the elderly. Lecithin cholesterol acyltransferase (LCAT) is an important enzyme responsible for lipid metabolism, which could be regulated by DNA methylation during the development of various age-related diseases. This study aimed to assess the association between LCAT DNA methylation and the risk of AMD, and to examine whether plasma vitamin and carotenoid concentrations modified this association. A total of 126 cases of AMD and 174 controls were included in the present analysis. LCAT DNA methylation was detected by quantitative real-time methylation-1specific PCR (qMSP). Circulating vitamins and carotenoids were measured using reversed-phase high-performance liquid chromatography (RP-HPLC). DNA methylation of LCAT was significantly higher in patients with AMD than those in the control subjects. After multivariable adjustment, participants in the highest tertile of LCAT DNA methylation had a 5.37-fold higher risk (95% CI: 2.56, 11.28) of AMD compared with those in the lowest tertile. Each standard deviation (SD) increment of LCAT DNA methylation was associated with a 2.23-fold (95% CI: 1.58, 3.13) increased risk of AMD. There was a J-shaped association between LCAT DNA methylation and AMD risk (P = 0.03). Higher concentrations of plasma retinol and β-cryptoxanthin were significantly associated with decreased levels of LCAT DNA methylation, with the multivariate-adjusted β coefficient being -0.05 (95% CI: -0.08, -0.01) and -0.25 (95% CI: -0.42, -0.08), respectively. In joint analyses of LCAT DNA methylation and plasma vitamin and carotenoid concentrations, the inverse association between increased LCAT DNA methylation and AMD risk was more pronounced among participants who had a lower concentration of plasma retinol and β-cryptoxanthin. These findings highlight the importance of comprehensively assessing LCAT DNA methylation and increasing vitamin and carotenoid status for the prevention of AMD.
Topics: Humans; Aged; Vitamins; Carotenoids; Vitamin A; Phosphatidylcholine-Sterol O-Acyltransferase; DNA Methylation; Beta-Cryptoxanthin; Macular Degeneration; Vitamin K
PubMed: 37447314
DOI: 10.3390/nu15132985 -
Cells Jan 2022Retinoic acid (RA) functions as an essential signal for development of the vertebrate eye by controlling the transcriptional regulatory activity of RA receptors (RARs).... (Review)
Review
Retinoic acid (RA) functions as an essential signal for development of the vertebrate eye by controlling the transcriptional regulatory activity of RA receptors (RARs). During eye development, the optic vesicles and later the retina generate RA as a metabolite of vitamin A (retinol). Retinol is first converted to retinaldehyde by retinol dehydrogenase 10 (RDH10) and then to RA by all three retinaldehyde dehydrogenases (ALDH1A1, ALDH1A2, and ALDH1A3). In early mouse embryos, RA diffuses to tissues throughout the optic placode, optic vesicle, and adjacent mesenchyme to stimulate folding of the optic vesicle to form the optic cup. RA later generated by the retina is needed for further morphogenesis of the optic cup and surrounding perioptic mesenchyme; loss of RA at this stage leads to microphthalmia and cornea plus eyelid defects. RA functions by binding to nuclear RARs at RA response elements (RAREs) that either activate or repress transcription of key genes. Binding of RA to RARs regulates recruitment of transcriptional coregulators such as nuclear receptor coactivator (NCOA) or nuclear receptor corepressor (NCOR), which in turn control binding of the generic coactivator p300 or the generic corepressor PRC2. No genes have been identified as direct targets of RA signaling during eye development, so future studies need to focus on identifying such genes and their RAREs. Studies designed to learn how RA normally controls eye development in vivo will provide basic knowledge valuable for determining how developmental eye defects occur and for improving strategies to treat eye defects.
Topics: Animals; Mice; Organogenesis; Retina; Retinaldehyde; Tretinoin; Vitamin A
PubMed: 35159132
DOI: 10.3390/cells11030322 -
Nutrients Jun 2023This study aimed to assess associations between forms of vitamin A and E (both individually and collectively) and the risk of prostate cancer, as well as identify...
PURPOSE
This study aimed to assess associations between forms of vitamin A and E (both individually and collectively) and the risk of prostate cancer, as well as identify potential effect modifiers.
METHODS
Utilizing data from the Singapore Prostate Cancer Study, a hospital-based case-control study, we measured the serum concentrations of 15 different forms of vitamins A and E in 156 prostate cancer patients and 118 control subjects, using a high-performance liquid chromatography technique. These forms included retinol, lutein, zeaxanthin, α-cryptoxanthin, β-cryptoxanthin, α-carotene, β-carotene, lycopene, ubiquinone, δ-tocopherol, γ-tocopherol, α-tocopherol, δ-tocotrienol, γ-tocotrienol, and α-tocotrienol. The odds ratio and 95% confidence interval for associations between vitamin A and E and prostate cancer risk were estimated using logistic regression models after adjustment for potential confounders. The analyses were further stratified by smoking and alcohol consumption status. The mixture effect of micronutrient groups was evaluated using weighted quantile sum regression.
RESULTS
Higher concentrations of retinol, lutein, α-carotene, β-carotene, ubiquinone, α-tocopherol, δ-tocotrienol, γ-tocotrienol, and α-tocotrienol were significantly and positively associated with overall prostate cancer risk. Among ever-smokers, associations were stronger for lutein, β-cryptoxanthin and β-carotene compared with never-smokers. Among regular alcohol drinkers, associations were stronger for lutein, β-cryptoxanthin, ubiquinone, γ-tocotrienol and α-tocotrienol compared with non-regular alcohol drinkers. Retinol and α-tocotrienol contributed most to the group indices 'vitamin A and provitamin A carotenoids' and 'vitamin E', respectively.
CONCLUSIONS
Several serum vitamin A and E forms were associated with prostate cancer risk, with significant effect modification by smoking and alcohol consumption status. Our findings shed light on prostate cancer etiology.
Topics: Male; Humans; Vitamin A; beta Carotene; Tocotrienols; Lutein; alpha-Tocopherol; Beta-Cryptoxanthin; Ubiquinone; Case-Control Studies; Singapore; Prostatic Neoplasms
PubMed: 37375581
DOI: 10.3390/nu15122677 -
Nutrients Mar 2022Naturally occurring retinoids (retinol, retinal, retinoic acid, retinyl esters) are a subclass of β-apocarotenoids, defined by the length of the polyene side chain.... (Review)
Review
Naturally occurring retinoids (retinol, retinal, retinoic acid, retinyl esters) are a subclass of β-apocarotenoids, defined by the length of the polyene side chain. Provitamin A carotenoids are metabolically converted to retinal (β-apo-15-carotenal) by the enzyme β-carotene-15,15'-dioxygenase (BCO1) that catalyzes the oxidative cleavage of the central C=C double bond. A second enzyme β-carotene-9'-10'-dioxygenase cleaves the 9',10' bond to yield β-apo-10'-carotenal and β-ionone. Chemical oxidation of the other double bonds leads to the generation of other β-apocarotenals. Like retinal, some of these β-apocarotenals are metabolically oxidized to the corresponding β-apocarotenoic acids or reduced to the β-apocarotenols, which in turn are esterified to β-apocarotenyl esters. Other metabolic fates such as 5,6-epoxidation also occur as for retinoids. Whether the same enzymes are involved remains to be understood. β-Apocarotenoids occur naturally in plant-derived foods and, therefore, are present in the diet of animals and humans. However, the levels of apocarotenoids are relatively low, compared with those of the parent carotenoids. Moreover, human studies show that there is little intestinal absorption of intact β-apocarotenoids. It is possible that they are generated in vivo under conditions of oxidative stress. The β-apocarotenoids are structural analogs of the naturally occurring retinoids. As such, they may modulate retinoid metabolism and signaling. In deed, those closest in size to the C-20 retinoids-namely, β-apo-14'-carotenoids (C-22) and β-apo-13-carotenone (C-18) bind with high affinity to purified retinoid receptors and function as retinoic acid antagonists in transactivation assays and in retinoic acid induction of target genes. The possible pathophysiologic relevance in human health remains to be determined.
Topics: Animals; Carotenoids; Dioxygenases; Humans; Retinoids; Tretinoin; beta Carotene; beta-Carotene 15,15'-Monooxygenase
PubMed: 35406024
DOI: 10.3390/nu14071411 -
Postepy Biochemii Mar 2023The skin aging process is affected by multiple different factors (including sun exposure, smoking, poor diet) and reactive oxygen species (ROS). Under their influence,...
The skin aging process is affected by multiple different factors (including sun exposure, smoking, poor diet) and reactive oxygen species (ROS). Under their influence, the skin becomes weaker, mainly elastin and collagen fibers are damaged. The amount of lipids is also reduced, leading to the death of the skin cells. The presence of free radicals also blocks the natural ability of the epidermis to regenerate. Each of these factors determines the acceleration of the signs of aging. To some extent, our body is able to deal with the free radicals by producing antioxidants. Regular supplementation is also a beneficial solution. Lycopene is a red pigment naturally found in tomatoes and is a known antioxidant. Among the carotenoids, it is the strongest singlet oxygen quencher and scavenger of peroxygen radicals, making it an important defense mechanism in the human body. The aim of this paper is to present the biological properties of lycopene in relation to its beneficial effect on the aging process of the skin.
Topics: Humans; Lycopene; Skin Aging; Carotenoids; Antioxidants; Free Radicals; Dietary Supplements
PubMed: 37493553
DOI: 10.18388/pb.2021_482 -
Drug Design, Development and Therapy 2023Vulvovaginal candidiasis (VVC) is experienced by an estimated 75% of women at least once in their lifetime and is recurrent, defined as three or more infections per year... (Review)
Review
Vulvovaginal candidiasis (VVC) is experienced by an estimated 75% of women at least once in their lifetime and is recurrent, defined as three or more infections per year (RVVC) in 5-9%. Candida albicans is the most common causative agent, but up to 19% of infections may be related to non-albicans species. Available treatment options for VVC have consisted of oral and topical azoles (except for topical nystatin, a polyene). Oral polyenes are not absorbed and therefore not effective for VVC. Fluconazole is the only oral medication FDA approved for VVC. None of these treatments are FDA approved for RVVC. Ibrexafungerp, a triterpenoid fungicidal agent, was FDA approved in 2021, becoming the first oral non-azole agent for VVC. Ibrexafungerp reaches concentrations up to 9-fold higher in vaginal tissues versus plasma. In Phase 2 clinical trials, ibrexafungerp had a clinical cure rate comparable to fluconazole at day 10, but significantly better at day 25. In Phase 3 clinical trials, ibrexafungerp had both a higher clinical and mycologic cure rate versus placebo at both days 10 and 25. In December 2022, Ibrexafungerp received FDA approval for once monthly dosing to decrease the incidence of RVVC. This approval was based on data from the CANDLE STUDY, which showed 65.4% resolution of symptoms and culture negative success through week 24, compared to 53.1% of placebo. Ibrexafungerp provides an alternative oral option for treatment of acute, severe VVC. It is the only FDA approved antifungal for RVVC. Currently, the population likely to benefit from this drug are those with azole allergy, non-albicans or azole resistant albicans species, or other azole contraindications such as drug interactions (like statins or tricyclics). Side effects are mostly gastrointestinal and mild in nature. Ibrexafungerp, like fluconazole, should be used with caution in women who are or may become pregnant.
Topics: Pregnancy; Female; Humans; Candidiasis, Vulvovaginal; Fluconazole; Antifungal Agents; Triterpenes; Candida albicans; Azoles; Polyenes
PubMed: 36785761
DOI: 10.2147/DDDT.S339349 -
Free Radical Research May 2015β-Carotene, the precursor of vitamin A, possesses pronounced radical scavenging properties. This has centered the attention on β-carotene dietary supplementation in... (Review)
Review
β-Carotene, the precursor of vitamin A, possesses pronounced radical scavenging properties. This has centered the attention on β-carotene dietary supplementation in healthcare as well as in the therapy of degenerative disorders and several cancer types. However, two intervention trials with β-carotene have revealed adverse effects on two proband groups, that is, cigarette smokers and asbestos-exposed workers. Beside other causative reasons, the detrimental effects observed have been related to the oxidation products of β-carotene. Their generation originates in the polyene structure of β-carotene that is beneficial for radical scavenging, but is also prone to oxidation. Depending on the dominant degradation mechanism, bond cleavage might occur either randomly or at defined positions of the conjugated electron system, resulting in a diversity of cleavage products (CPs). Due to their instability and hydrophobicity, the handling of standards and real samples containing β-carotene and related CPs requires preventive measures during specimen preparation, analyte extraction, and final analysis, to avoid artificial degradation and to preserve the initial analyte portfolio. This review critically discusses different preparation strategies of standards and treatment solutions, and also addresses their protection from oxidation. Additionally, in vitro oxidation strategies for the generation of oxidative model compounds are surveyed. Extraction methods are discussed for volatile and non-volatile CPs individually. Gas chromatography (GC), (ultra)high performance liquid chromatography (U)HPLC, and capillary electrochromatography (CEC) are reviewed as analytical tools for final analyte analysis. For identity confirmation of analytes, mass spectrometry (MS) is indispensable, and the appropriate ionization principles are comprehensively discussed. The final sections cover analysis of real samples and aspects of quality assurance, namely matrix effects and method validation.
Topics: Animals; Biological Assay; Calibration; Cells, Cultured; Chemistry Techniques, Analytical; Drug Stability; Free Radical Scavengers; Humans; Hydrophobic and Hydrophilic Interactions; Molecular Structure; Oxidants; Oxidation-Reduction; Reference Standards; Solubility; Structure-Activity Relationship; beta Carotene
PubMed: 25867077
DOI: 10.3109/10715762.2015.1022539 -
Marine Drugs Feb 2023Microalgae are the richest source of natural carotenoids, which are valuable pigments with a high share of benefits. Often, carotenoid-producing algae inhabit specific... (Review)
Review
Microalgae are the richest source of natural carotenoids, which are valuable pigments with a high share of benefits. Often, carotenoid-producing algae inhabit specific biotopes with unfavorable or even extremal conditions. Such biotopes, including alpine snow fields and hypersaline ponds, are widely distributed in Europe. They can serve as a source of new strains for biotechnology. The number of algal species used for obtaining these compounds on an industrial scale is limited. The data on them are poor. Moreover, some of them have been reported in non-English local scientific articles and theses. This review aims to summarize existing data on microalgal species, which are known as potential carotenoid producers in biotechnology. These include and , both well-known to the scientific community, as well as less-elucidated representatives. Their distribution will be covered throughout Europe: from the Greek Mediterranean coast in the south to the snow valleys in Norway in the north, and from the ponds in Amieiro (Portugal) in the west to the saline lakes and mountains in Crimea (Ukraine) in the east. A wide spectrum of algal secondary carotenoids is reviewed: β-carotene, astaxanthin, canthaxanthin, echinenone, adonixanthin, and adonirubin. For convenience, the main concepts of biology of carotenoid-producing algae are briefly explained.
Topics: Carotenoids; beta Carotene; Chlorophyceae; Biotechnology; Europe
PubMed: 36827149
DOI: 10.3390/md21020108 -
Marine Drugs Apr 2022Fucoxanthin, belonging to the xanthophyll class of carotenoids, is a natural antioxidant pigment of marine algae, including brown macroalgae and diatoms. It represents... (Review)
Review
Fucoxanthin, belonging to the xanthophyll class of carotenoids, is a natural antioxidant pigment of marine algae, including brown macroalgae and diatoms. It represents 10% of the total carotenoids in nature. The plethora of scientific evidence supports the potential benefits of nutraceutical and pharmaceutical uses of fucoxanthin for boosting human health and disease management. Due to its unique chemical structure and action as a single compound with multi-targets of health effects, it has attracted mounting attention from the scientific community, resulting in an escalated number of scientific publications from January 2017 to February 2022. Fucoxanthin has remained the most popular option for anti-cancer and anti-tumor activity, followed by protection against inflammatory, oxidative stress-related, nervous system, obesity, hepatic, diabetic, kidney, cardiac, skin, respiratory and microbial diseases, in a variety of model systems. Despite much pharmacological evidence from in vitro and in vivo findings, fucoxanthin in clinical research is still not satisfactory, because only one clinical study on obesity management was reported in the last five years. Additionally, pharmacokinetics, safety, toxicity, functional stability, and clinical perspective of fucoxanthin are substantially addressed. Nevertheless, fucoxanthin and its derivatives are shown to be safe, non-toxic, and readily available upon administration. This review will provide pharmacological insights into fucoxanthin, underlying the diverse molecular mechanisms of health benefits. However, it requires more activity-oriented translational research in humans before it can be used as a multi-target drug.
Topics: Carotenoids; Humans; Neoplasms; Seaweed; Xanthophylls
PubMed: 35621930
DOI: 10.3390/md20050279 -
European Journal of Nutrition Aug 2022Carotenoids may protect against chronic diseases including cancer and cardiometabolic disease by mitigating oxidative stress and/or inflammation. We cross-sectionally...
PURPOSE
Carotenoids may protect against chronic diseases including cancer and cardiometabolic disease by mitigating oxidative stress and/or inflammation. We cross-sectionally evaluated associations between carotenoids and biomarkers of oxidative stress or inflammation.
METHODS
From 2003 to 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35-74. Post-menopausal participants (n = 512) were randomly sampled to measure carotenoids and biomarkers of oxidative stress. Dietary carotenoid consumption was assessed using a validated 110-item Block 1998 food frequency questionnaire; use of β-carotene-containing supplements was also assessed. Plasma carotenoids were quantified, adjusting for batch. Urinary markers of lipid peroxidation, 8-iso-prostaglandin F (8-iso-PGF) and its metabolite (8-iso-PGF-M) were also measured. Since the biomarker 8-iso-PGF can reflect both oxidative stress and inflammation, we used a modeled 8-iso-PGF to prostaglandin F ratio approach to distinguish effects reflecting oxidative stress versus inflammation. Multivariable linear regression was used to assess the associations of dietary and plasma carotenoids with the estimated biomarker concentrations.
RESULTS
Total plasma carotenoids were inversely associated with 8-iso-PGF-M concentrations (P for trend across quartiles = 0.009). Inverse trends associations were also seen for α-carotene and β-carotene. In contrast, lutein/zeaxanthin showed associations with both 8-iso-PGF and 8-iso-PGF-M concentrations. The inverse association for total carotenoids appeared to be specific for oxidative stress (chemical 8-iso-PGF; P = 0.04 and P for trend across quartiles = 0.02). The pattern was similar for α-carotene. However, lutein/zeaxanthin tended to have a stronger association with enzymatic 8-iso-PGF, suggesting an additional anti-inflammatory effect. Supplemental β-carotene was inversely associated with both 8-iso-PGF and 8-iso-PGF-M concentrations, as well as with both chemical and enzymatic 8-iso-PGF. Dietary carotenoids were not associated with either biomarker.
CONCLUSION
Plasma carotenoids and supplemental β-carotene were associated with lower concentrations of 8-iso-PGF metabolite. Plasma carotenoids associations may reflect antioxidant effects.
Topics: Biomarkers; Carotenoids; Dinoprost; F2-Isoprostanes; Female; Humans; Inflammation; Isoprostanes; Lutein; Oxidative Stress; Zeaxanthins; beta Carotene
PubMed: 35253072
DOI: 10.1007/s00394-022-02837-8