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Advances in Nutrition (Bethesda, Md.) Nov 2023Carotenoids have been associated with risk reduction for several chronic diseases, including the association of their dietary intake/circulating levels with reduced... (Review)
Review
Carotenoids have been associated with risk reduction for several chronic diseases, including the association of their dietary intake/circulating levels with reduced incidence of obesity, type 2 diabetes, certain types of cancer, and even lower total mortality. In addition to some carotenoids constituting vitamin A precursors, they are implicated in potential antioxidant effects and pathways related to inflammation and oxidative stress, including transcription factors such as nuclear factor κB and nuclear factor erythroid 2-related factor 2. Carotenoids and metabolites may also interact with nuclear receptors, mainly retinoic acid receptor/retinoid X receptor and peroxisome proliferator-activated receptors, which play a role in the immune system and cellular differentiation. Therefore, a large number of downstream targets are likely influenced by carotenoids, including but not limited to genes and proteins implicated in oxidative stress and inflammation, antioxidation, and cellular differentiation processes. Furthermore, recent studies also propose an association between carotenoid intake and gut microbiota. While all these endpoints could be individually assessed, a more complete/integrative way to determine a multitude of health-related aspects of carotenoids includes (multi)omics-related techniques, especially transcriptomics, proteomics, lipidomics, and metabolomics, as well as metagenomics, measured in a variety of biospecimens including plasma, urine, stool, white blood cells, or other tissue cellular extracts. In this review, we highlight the use of omics technologies to assess health-related effects of carotenoids in mammalian organisms and models.
Topics: Animals; Humans; Carotenoids; Diabetes Mellitus, Type 2; Inflammation; Antioxidants; Lutein; Mammals
PubMed: 37678712
DOI: 10.1016/j.advnut.2023.09.002 -
Pharmacological Reports : PR Aug 2023Astaxanthin (AXT) is a red fat-soluble pigment found naturally in aquatic animals, plants, and various microorganisms and can be manufactured artificially using chemical... (Review)
Review
Astaxanthin (AXT) is a red fat-soluble pigment found naturally in aquatic animals, plants, and various microorganisms and can be manufactured artificially using chemical catalysis. AXT is a xanthophyll carotenoid with a high potential for scavenging free radicals. Several studies have investigated AXT efficacy against diseases such as neurodegenerative, ocular, skin, and cardiovascular hypertension, diabetes, gastrointestinal and liver diseases, and immuno-protective functions. However, its poor solubility, low stability to light and oxygen, and limited bioavailability are major obstacles hindering its wide applications as a therapeutic agent or nutritional supplement. Incorporating AXT with nanocarriers holds great promise in enhancing its physiochemical properties. Nanocarriers are delivery systems with several benefits, including surface modification, bioactivity, and targeted medication delivery and release. Many approaches have been applied to enhance AXT's medicinal effect, including solid lipid nanoparticles, nanostructured lipid carriers (NLCs) and polymeric nanospheres. AXT nano-formulations have demonstrated a high antioxidant and anti-inflammatory effect, significantly affecting cancer in different organs. This review summarizes the most recent data on AXT production, characterization, biological activity, and therapeutic usage, focusing on its uses in the nanotechnology era.
Topics: Animals; Antioxidants; Xanthophylls; Dietary Supplements; Nanotechnology
PubMed: 37179259
DOI: 10.1007/s43440-023-00488-y -
Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta.Genetics in Medicine : Official Journal... Aug 2023Dominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth...
PURPOSE
Dominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12.
METHODS
We used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids.
RESULTS
We found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity. Loss-of-function variants disrupted RARB function through a dominant-negative effect, possibly by disrupting ligand binding and/or coactivators' recruitment. By reviewing clinical data from 52 affected individuals, we found that disruption of RARB is associated with a more variable phenotype than initially suspected, with the absence in some individuals of cardinal features of MCOPS12, such as developmental eye anomaly or motor impairment.
CONCLUSION
Our study indicates that pathogenic variants in RARB are functionally heterogeneous and associated with extensive clinical heterogeneity.
Topics: Humans; Receptors, Retinoic Acid; Retinoids; Microphthalmos
PubMed: 37092537
DOI: 10.1016/j.gim.2023.100856 -
Notch and retinoic acid signals regulate macrophage formation from endocardium downstream of Nkx2-5.Nature Communications Sep 2023Hematopoietic progenitors are enriched in the endocardial cushion and contribute, in a Nkx2-5-dependent manner, to tissue macrophages required for the remodeling of...
Hematopoietic progenitors are enriched in the endocardial cushion and contribute, in a Nkx2-5-dependent manner, to tissue macrophages required for the remodeling of cardiac valves and septa. However, little is known about the molecular mechanism of endocardial-hematopoietic transition. In the current study, we identified the regulatory network of endocardial hematopoiesis. Signal network analysis from scRNA-seq datasets revealed that genes in Notch and retinoic acid (RA) signaling are significantly downregulated in Nkx2-5-null endocardial cells. In vivo and ex vivo analyses validate that the Nkx2-5-Notch axis is essential for the generation of both hemogenic and cushion endocardial cells, and the suppression of RA signaling via Dhrs3 expression plays important roles in further differentiation into macrophages. Genetic ablation study revealed that these macrophages are essential in cardiac valve remodeling. In summary, the study demonstrates that the Nkx2-5/Notch/RA signaling plays a pivotal role in macrophage differentiation from hematopoietic progenitors.
Topics: Endocardium; Macrophages; Histiocytes; Cell Differentiation; Tretinoin
PubMed: 37669937
DOI: 10.1038/s41467-023-41039-6 -
Biochemical Society Transactions Feb 2024Oxidative stress, an imbalance between pro-oxidant and antioxidant status, favouring the pro-oxidant state is a result of increased production of reactive oxygen species... (Review)
Review
Oxidative stress, an imbalance between pro-oxidant and antioxidant status, favouring the pro-oxidant state is a result of increased production of reactive oxygen species (ROS) or inadequate antioxidant protection. ROS are produced through several mechanisms in cells including during mitochondrial oxidative phosphorylation. Increased mitochondrial-derived ROS are associated with mitochondrial dysfunction, an early event in age-related diseases such as Alzheimer's diseases (ADs) and in metabolic disorders including diabetes. AD post-mortem investigations of affected brain regions have shown the accumulation of oxidative damage to macromolecules, and oxidative stress has been considered an important contributor to disease pathology. An increase in oxidative stress, which leads to increased levels of superoxide, hydrogen peroxide and other ROS in a potentially vicious cycle is both causative and a consequence of mitochondrial dysfunction. Mitochondrial dysfunction may be ameliorated by molecules with antioxidant capacities that accumulate in mitochondria such as carotenoids. However, the role of carotenoids in mitigating mitochondrial dysfunction is not fully understood. A better understanding of the role of antioxidants in mitochondrial function is a promising lead towards the development of novel and effective treatment strategies for age-related diseases. This review evaluates and summarises some of the latest developments and insights into the effects of carotenoids on mitochondrial dysfunction with a focus on the antioxidant properties of carotenoids. The mitochondria-protective role of carotenoids may be key in therapeutic strategies and targeting the mitochondria ROS is emerging in drug development for age-related diseases.
Topics: Humans; Antioxidants; Reactive Oxygen Species; Carotenoids; Oxidative Stress; Mitochondrial Diseases
PubMed: 38385583
DOI: 10.1042/BST20230193 -
Journal of ISAKOS : Joint Disorders &... Oct 2023Anatomical total shoulder arthroplasty in its modern form where it reproduces the normal shoulder has been utilized clinically for more than half a century. As the... (Review)
Review
Anatomical total shoulder arthroplasty in its modern form where it reproduces the normal shoulder has been utilized clinically for more than half a century. As the technology and the designs have changed to recreate the humeral and glenoid sides of the joint, the sophistication of design has resulted in the growing number of cases annually worldwide. This increase is due in part to the increasing number of indications that the prosthesis can treat with successful results. On the humeral side, there have been design changes to better reflect the proximal humeral anatomy, and humeral stems are increasingly placed safely without cement. Platform systems which allow conversion of a failed arthroplasty to a reverse configuration without stem extraction is another design change. Similarly, there has been increasing utilization of short stem and stemless humeral components. Extensive experience with shorter stem and stemless devices, however, has yet to demonstrate the purported advantages of these devices, as recent studies have demonstrated equivalent blood loss, fracture rates, operative times, and outcome scores. Easier revision with these shorter stems remains to be definitively established, with only one study comparing the ease of revision between stem types. On the glenoid side, hybrid cementless glenoids, inlay glenoids, cementless all-polyethylene glenoids, and augmented glenoids have all been investigated; however, the indications for these devices remain unclear. Lastly, innovative surgical approaches to implanting shoulder arthroplasty and the use of patient specific guides and computerized planning, while interesting concepts, still await validation before they are utilized on a widespread basis. While reverse shoulder arthroplasty has been increasingly used to reconstruct the arthritic shoulder, anatomic glenohumeral replacement maintains a significant role in the armamentarium of the shoulder surgeon.
Topics: Humans; Prosthesis Design; Arthroplasty, Replacement, Shoulder; Joint Prosthesis; Shoulder Prosthesis; Polyethylene
PubMed: 37207983
DOI: 10.1016/j.jisako.2023.05.001 -
Marine Drugs Dec 2023Crocin is one of the most valuable components of the Chinese medicinal plant and is widely used in the food, cosmetics, and pharmaceutical industries. Traditional... (Review)
Review
Crocin is one of the most valuable components of the Chinese medicinal plant and is widely used in the food, cosmetics, and pharmaceutical industries. Traditional planting of is unable to fulfill the increasing demand for crocin in the global market, however, such that researchers have turned their attention to the heterologous production of crocin in a variety of hosts. At present, there are reports of successful heterologous production of crocin in , , microalgae, and plants that do not naturally produce crocin. Of these, the microalga , which produces high levels of -carotene, the substrate for crocin biosynthesis, is worthy of attention. This article describes the biosynthesis of crocin, compares the features of each heterologous host, and clarifies the requirements for efficient production of crocin in microalgae.
Topics: Carotenoids; beta Carotene; Chlorophyceae; Drug Industry; Escherichia coli; Microalgae; Saccharomyces cerevisiae
PubMed: 38248646
DOI: 10.3390/md22010022 -
BMC Public Health Aug 2023Dietary carotenoids have been proven to improve intestinal disorders like inflammatory bowel disease and colon cancer, yet little is known about the link between dietary...
BACKGROUND
Dietary carotenoids have been proven to improve intestinal disorders like inflammatory bowel disease and colon cancer, yet little is known about the link between dietary carotenoids and constipation. This study aims to examine the relationship between dietary carotenoids intake and constipation, using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2010.
METHODS
A total of 11,722 participants were enrolled. Chronic constipation was defined as type 1 (separate hard lumps, like nuts) and type 2 (sausage-like, but lumpy) in the Bristol stool form scale (BSFS). Carotenoids intake was obtained from the average of two 24-hour dietary recall questionnaires (if only one 24-hour was available, we used it) and divided into quartiles (Q). The prevalence of constipation was calculated across men and women individuals. The relationship between dietary carotenoids intake and constipation in men and women was assessed with weighted logistic regression and smoothed curve fitting after adjusting confounders, with results displayed as weighted odds ratio (OR) with 95% confidence intervals (95% CI). The model was further stratified by age, race, and HEI 2015 scores (with median as cutoff) among men and women.
RESULTS
The total weighted prevalence of chronic constipation in this study was 8.08%, 11.11% in women and 5.18% in men. After multivariable adjustment, compared with the lowest intake, participants with the highest dietary lycopene intake (OR 0.55, 95% CI: 0.36-0.84, p for trend = 0.01) and total lycopene intake (OR = 0.52, 95% CI: 0.34-0.80, p for trend = 0.01) were negatively associated with the risk of chronic constipation in men, whereas increased dietary α-carotene intake reduced the risk of chronic constipation in women (OR = 0.69, 95% CI: 0.48-0.98, p for trend = 0.04). Smoothing curve fitting further supported these results and provided evidence of dose-response effects. No association was found between other types of carotenoids and chronic constipation in men and women.
CONCLUSIONS
Increasing lycopene intake may improve bowel function in men while increased α-carotene intake may reduce the risk of chronic constipation in women. Further studies are essential to explore the role that the intake of carotenoids plays in chronic constipation.
Topics: Male; Adult; Female; Humans; Lycopene; Cross-Sectional Studies; Nutrition Surveys; Carotenoids; Constipation
PubMed: 37608273
DOI: 10.1186/s12889-023-16367-3 -
Theranostics 2023The potentially unlimited number of cardiomyocyte (CMs) derived from human induced pluripotent stem cells (hiPSCs) facilitates high throughput applications like cell...
The potentially unlimited number of cardiomyocyte (CMs) derived from human induced pluripotent stem cells (hiPSCs) facilitates high throughput applications like cell transplantation for myocardial repair, disease modelling, and cardiotoxicity testing during drug development. Despite promising progress in these areas, a major disadvantage that limits the use of hiPSC derived CMs (hiPSC-CMs) is their immaturity. : Three hiPSC lines (PCBC-hiPSC, DP3-hiPSCs, and MLC2v-mEGFP hiPSC) were differentiated into CMs (PCBC-CMs, DP3-CMs, and MLC2v-CMs, respectively) with or without retinoic acid (RA). hiPSC-CMs were either maintained up to day 30 of contraction (D30C), or D60C, or purified using lactate acid and used for experiments. Purified hiPSC-CMs were cultured in basal maturation medium (BMM) or BMM supplemented with ascorbic acid (AA) for 14 days. The AA treated and non-treated hiPSC-CMs were characterized for sarcomeric proteins (MLC2v, TNNI3, and MYH7), ion channel proteins (Kir2.1, Nav1.5, Cav1.2, SERCA2a, and RyR), mitochondrial membrane potential, metabolomics, and action potential. Bobcat339, a selective and potent inhibitor of DNA demethylation, was used to determine whether AA promoted hiPSC-CM maturation through modulating DNA demethylation. AA significantly increased MLC2v expression in PCBC-CMs, DP3-CMs, MLC2v-CMs, and RA induced atrial-like PCBC-CMs. AA treatment significantly increased mitochondrial mass, membrane potential, and amino acid and fatty acid metabolism in PCBC-CMs. Patch clamp studies showed that AA treatment induced PCBC-CMs and DP3-CMs adaptation to a ventricular-like phenotype. Bobcat339 inhibited MLC2v protein expression in AA treated PCBC-CMs and DP3-CMs. DNA demethylation inhibition was also associated with reduced TET1 and TET2 protein expressions and reduced accumulation of the oxidative product, 5 hmC, in both PCBC-CMs and DP3-CMs, in the presence of AA. Ascorbic acid induced MLC2v protein expression and promoted ventricular-like CM subtype in hiPSC-CMs. The effect of AA on hiPSC-CM was attenuated with inhibition of TET1/TET2 mediated DNA demethylation.
Topics: Humans; Induced Pluripotent Stem Cells; Ascorbic Acid; Myocytes, Cardiac; Cell Differentiation; Tretinoin; Cells, Cultured; Mixed Function Oxygenases; Proto-Oncogene Proteins
PubMed: 37441603
DOI: 10.7150/thno.80801 -
Journal of Obstetrics and Gynaecology :... Dec 2023This study was designed to investigate the association between nutrients and female infertility.
BACKGROUND
This study was designed to investigate the association between nutrients and female infertility.
METHODS
A cross-sectional study on 18-45 years of age reproductive-age women was conducted using the data from the National Health and Nutrition Examination Surveys (NHANES) for the periods 2013-2014 and 2015-2016. Multivariate logistic regression analysis was performed to evaluate the association between nutrients and female infertility. Subgroup analysis was applied to the body mass index (BMI). Results were summarised using an odds ratio (OR) with a 95% confidence interval (CI).
RESULTS
Of the total 1713 women, 204 women (11.91%) were infertile. The result demonstrated that higher intake of carbohydrate (OR: 0.46, 95% CI: 0.24-0.86, = 0.018), vitamin A (OR: 0.44, 95% CI: 0.24-0.80, = 0.009), vitamin C (OR: 0.48, 95% CI: 0.26-0.88, = 0.020), magnesium (OR: 0.36, 95% CI: 0.17-0.76, = 0.009), iron (OR: 0.43, 95% CI: 0.23-0.82, = 0.012), lycopene (OR: 0.55, 95% CI: 0.33-0.91, = 0.022), and total folate (OR: 0.38, 95% CI: 0.20-0.70, = 0.003) were associated with a lower risk of female infertility. The subgroup analysis also reported that intakes of vitamin A, vitamin C, and lycopene were related to a lower risk of female infertility among women with a BMI being 18.5-24.9 kg/m. Among women with BMI > 24.9 kg/m, high intakes of magnesium, iron and total folate were associated with a decreased risk of female infertility.
CONCLUSIONS
The intake of several nutrients is associated with a decreased risk of female infertility. These findings provide insight into potentially modifiable lifestyle factors associated with female infertility.
Topics: Female; Humans; Diet; Nutrition Surveys; Magnesium; Vitamin A; Infertility, Female; Cross-Sectional Studies; Lycopene; Eating; Vitamins; Folic Acid; Ascorbic Acid; Iron
PubMed: 38010776
DOI: 10.1080/01443615.2023.2285025