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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 -
Clinical Nutrition (Edinburgh, Scotland) Dec 2023Optimal maternal vitamin status during pregnancy and lactation is essential to support maternal and infant health. For instance, vitamin D is involved in infant bone... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Optimal maternal vitamin status during pregnancy and lactation is essential to support maternal and infant health. For instance, vitamin D is involved in infant bone development, and B-vitamins are involved in various metabolic processes, including energy production. Through a double-blind randomised controlled trial, we investigated the effects of maternal supplementation from preconception throughout pregnancy until birth on human milk (HM) concentrations of vitamin D and B-vitamins. In addition, we aimed to characterise longitudinal changes in milk concentrations of these vitamins.
METHODS
Both control and intervention supplements contained calcium, iodine, iron, β-carotene, and folic acid, while the intervention also contained zinc, vitamins B, B, B, and D, probiotics, and myo-inositol. HM samples were collected across 4 time points from 1 week to 3 months post-delivery from 158 mothers in Singapore, and 7 time points from 1 week to 12 months from 180 mothers in New Zealand. HM vitamin D was quantified using supercritical fluid chromatography and B-vitamins with mass spectrometry. Potential intervention effects on HM vitamins D, B, B, and B, as well as other B-vitamin (B and B) concentrations were assessed using linear mixed models with a repeated measures design.
RESULTS
Over the first 3 months of lactation, HM 25-hydroxyvitamin D concentrations were 20% (95% CI 8%, 33%, P = 0.001) higher in the intervention group, with more marked effects in New Zealand. There were no observed intervention effects on HM concentrations of vitamins B, B, B, B, and B. In New Zealand mothers, longitudinally, vitamin D concentrations gradually increased from early lactation up to 12 months, while vitamins B and B peaked at 6 weeks, B at 3 weeks, and B and B at 3 months.
CONCLUSIONS
Maternal supplementation during preconception and pregnancy increased HM vitamin D, but not B-vitamin concentrations in lactation. Further studies are required to examine the discrete benefits of vitamin D supplementation starting preconception vs during pregnancy, and to further characterise the effects of supplementation on later offspring health outcomes.
CLINICAL TRIAL REGISTRATION
Registered at ClinicalTrials.gov on the 16 July 2015 (identifier NCT02509988); Universal Trial Number U1111-1171-8056. This study was academic-led by the EpiGen Global Research Consortium.
Topics: Pregnancy; Infant; Female; Humans; Vitamins; Vitamin D; Milk, Human; Dietary Supplements; Cholecalciferol; Lactation; Vitamin A; Double-Blind Method
PubMed: 38411017
DOI: 10.1016/j.clnu.2023.09.009 -
International Journal of Molecular... Dec 2023Fat-soluble vitamins (vitamin A, D, E, and K) assume a pivotal role in maintaining human homeostasis by virtue of their enzymatic functions. The daily inclusion of these... (Review)
Review
Fat-soluble vitamins (vitamin A, D, E, and K) assume a pivotal role in maintaining human homeostasis by virtue of their enzymatic functions. The daily inclusion of these vitamins is imperative to the upkeep of various physiological processes including vision, bone health, immunity, and protection against oxidative stress. Current research highlights fat-soluble vitamins as potential therapeutics for human diseases, especially cancer. Fat-soluble vitamins exert their therapeutic effects through multiple pathways, including regulation of matrix metalloproteinases' (MMPs) expression and enzymatic activity. As MMPs have been reported to be involved in the pathology of various diseases, such as cancers, cardiovascular diseases, and neurological disorders, regulating the expression and/or activity of MMPs could be considered as a potent therapeutic strategy. Here, we summarize the properties of fat-soluble vitamins and their potential as promising candidates capable of effectively modulating MMPs through multiple pathways to treat human diseases.
Topics: Humans; Vitamin A; Matrix Metalloproteinase 2; Vitamins; Vitamin K; Cardiovascular Diseases; Vitamin D; Vitamin E
PubMed: 38069361
DOI: 10.3390/ijms242317038 -
Frontiers in Immunology 2023Invariant chain (Ii, CD74) is a type II transmembrane glycoprotein that acts as a chaperone and facilitates the folding and transport of MHC II chains. By assisting the...
Invariant chain (Ii, CD74) is a type II transmembrane glycoprotein that acts as a chaperone and facilitates the folding and transport of MHC II chains. By assisting the assembly and subcellular targeting of MHC II complexes, Ii has a wide impact on the functions of antigen-presenting cells such as antigen processing, endocytic maturation, signal transduction, cell migration, and macropinocytosis. Ii is a multifunctional molecule that can alter endocytic traffic and has several interacting molecules. To understand more about Ii's function and to identify further Ii interactors, a yeast two-hybrid screening was performed. Retinoic Acid-Induced 14 (Rai14) was detected as a putative interaction partner, and the interaction was confirmed by co-immunoprecipitation. Rai14 is a poorly characterized protein, which is believed to have a role in actin cytoskeleton and membrane remodeling. In line with this, we found that Rai14 localizes to membrane ruffles, where it forms macropinosomes. Depletion of Rai14 in antigen-presenting cells delays MHC II internalization, affecting macropinocytic activity. Intriguingly, we demonstrated that, similar to Ii, Rai14 is a positive regulator of macropinocytosis and a negative regulator of cell migration, two antagonistic processes in antigen-presenting cells. This antagonism is known to depend on the interaction between myosin II and Ii. Here, we show that Rai14 also binds to myosin II, suggesting that Ii, myosin II, and Rai14 work together to coordinate macropinocytosis and cell motility.
Topics: Tretinoin; Histocompatibility Antigens Class II; Pinocytosis; Cytoskeletal Proteins; Myosin Type II
PubMed: 37545539
DOI: 10.3389/fimmu.2023.1182180 -
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 -
Drugs Oct 2023Silencing the transthyretin (TTR) gene is an effective strategy in the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis. Vutrisiran (Amvuttra), an RNA... (Review)
Review
Silencing the transthyretin (TTR) gene is an effective strategy in the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis. Vutrisiran (Amvuttra), an RNA interference (RNAi) therapeutic targeting TTR mRNA, is approved in the USA and EU for the treatment of adults with polyneuropathy of hATTR amyloidosis. N-acetylgalactosamine conjugation and enhanced stabilisation chemistry are utilised to target vutrisiran to the liver and increase stability, respectively, allowing for subcutaneous administration once every 3 months. In a pivotal phase 3 study in patients with hATTR amyloidosis with polyneuropathy, subcutaneous vutrisiran 25 mg every 3 months significantly reduced neuropathy impairment versus external placebo. Vutrisiran was also associated with significant improvements in neuropathy-specific quality of life, gait speed, nutritional status and disability scores. Vutrisiran was generally well tolerated; the only common adverse events to occur at a greater incidence than with external placebo were pain in extremity and arthralgia. Vutrisiran reduces serum vitamin A levels and vitamin A supplementation is recommended. In conclusion, vutrisiran is an efficacious and generally well-tolerated alternative option for the treatment of polyneuropathy of hATTR amyloidosis, which has the potential advantage of infrequent subcutaneous dosage.
Topics: Adult; Humans; Quality of Life; Prealbumin; Vitamin A; Amyloid Neuropathies, Familial; Polyneuropathies
PubMed: 37728865
DOI: 10.1007/s40265-023-01943-z -
Annals of Medicine Dec 2023Vitamin A has multiple functions in the human body, being involved in growth, epithelial differentiation, vision, immune function and reproduction. While normal...
PURPOSE
Vitamin A has multiple functions in the human body, being involved in growth, epithelial differentiation, vision, immune function and reproduction. While normal spermatogenesis is influenced by several factors, it requires vitamin A. Systemic isotretinoin is a vitamin A derivative that is used in the treatment of many dermatological diseases, especially acne vulgaris (AV). There is limited research on the changes in semen parameters after systemic isotretinoin therapy in humans. Our study investigates the presence of varicoceles in patients undergoing systemic isotretinoin therapy for AV and examines whether there were any changes in the semen parameters before and after treatment.
METHODS
Included in the study were 46 men patients who were scheduled for systemic isotretinoin therapy for AV. Before treatment, the patients underwent a physical examination and ultrasonography for varicoceles assessment. The patients underwent spermiogram before treatment and after 6 months of treatment. The spermiogram assessments included semen volume, sperm concentration, total sperm count, progressive motility, viability and sperm morphology.
RESULTS
After treatment, there was an increase in semen volume, sperm concentration, total sperm count, progressive motility and vitality from the pre-treatment values, but a deterioration in the sperm morphology ( < .05). Comparing patients with and without varicoceles revealed more changes in semen parameters after treatment in those with varicoceles. There was a statistically significant difference in sperm concentration ( < .001).
CONCLUSIONS
Systemic isotretinoin therapy negatively affects sperm morphology, but has positive effect on other semen parameters, and these changes in semen parameters occur more frequently in patients with varicoceles.KEY MESSAGESAcne vulgaris is a very common disease and systemic isotretinoin is used as the most effective agent in its treatment.Systemic isotretinoin positively affects semen parameters except sperm morphology.Changes in semen parameters are more common in patients with varicocele.
Topics: Humans; Male; Semen; Isotretinoin; Infertility, Male; Varicocele; Vitamin A; Sperm Motility
PubMed: 37162375
DOI: 10.1080/07853890.2023.2207038 -
Nutrients Oct 2023Melanoma, a prevalent and lethal form of skin cancer, remains a formidable challenge in terms of prevention and treatment. While significant progress has been made in... (Review)
Review
Melanoma, a prevalent and lethal form of skin cancer, remains a formidable challenge in terms of prevention and treatment. While significant progress has been made in understanding its pathogenesis and treatment, the quest for effective prevention strategies and therapeutic approaches remains ongoing. Considering the increased advancements in understanding the dynamic interplay between nutrients and melanoma, we aim to offer a refreshed perspective on nutrient-based approaches for melanoma prevention and adjunctive therapy. In contrast to other studies, we have innovatively provided a detailed exposition of the nutrients' influences on melanoma prognosis and treatment. This review firstly examines various nutrients, including antioxidants (namely vitamins A, D, C, and E; selenium; and caffeine), polyunsaturated fatty acids, and flavonoids, for their effects and underlying mechanisms in reducing melanoma risk. Among these nutrients, caffeine shows the most promising potential, as it is supported by multiple cohort studies for its protective effect against melanoma. In contrast, there is a certain degree of inconsistency in the research of other nutrients, possibly due to inherent differences between animal studies and epidemiological research, as well as variations in the definition of nutrient intake. To comprehensively investigate the impact of nutrients on melanoma progression and therapeutic approaches, the following sections will explore how nutrients influence immune responses and other physiological processes. While there is robust support from cell and animal studies regarding the immunomodulatory attributes of vitamins D and zinc, the anti-angiogenic potential of polyphenols, and the cell growth-inhibitory effects of flavonoids, the limited availability of human-based research substantially constrains their practical relevance in clinical contexts. As for utilizing nutrients in adjuvant melanoma treatments, multiple approaches have garnered clinical research support, including the utilization of vitamin D to decrease the postoperative recurrence rates among melanoma patients and the adoption of a high-fiber diet to enhance the effectiveness of immunotherapy. In general, the effects of most nutrients on reducing the risk of melanoma are not entirely clear. However, several nutrients, including vitamin D and dietary fiber, have demonstrated their potential to improve the melanoma prognosis and enhance the treatment outcomes, making them particularly deserving of clinical attention. A personalized and interdisciplinary approach, involving dermatologists, oncologists, nutritionists, and researchers, holds the promise of optimizing melanoma treatment strategies.
Topics: Humans; Caffeine; Vitamins; Melanoma; Vitamin D; Vitamin A; Flavonoids; Diet
PubMed: 37892558
DOI: 10.3390/nu15204483 -
Journal of Renal Nutrition : the... Nov 2023This paper summarizes the biochemistry, metabolism, and dietary needs of vitamins in patients with chronic kidney disease (CKD) and kidney transplant recipients.... (Review)
Review
This paper summarizes the biochemistry, metabolism, and dietary needs of vitamins in patients with chronic kidney disease (CKD) and kidney transplant recipients. Evidence indicates that the dietary intake, in vivo synthesis, urinary excretion or metabolism of different vitamins may be substantially altered in kidney failure. There are discrepancies in vitamin status assessment depending on whether the assay is functional or measuring the blood vitamin level. Whether vitamin supplements should be routinely prescribed for patients with CKD is controversial. Because low dietary intake and compounds that interfere with vitamin activity are not uncommon in patients with CKD, and water-soluble vitamin supplements appear safe and not costly, the authors recommend that supplements of the water-soluble vitamins should be routinely offered to these individuals. More research is needed to assess vitamin nutrition and function and to determine the daily vitamin needs for all patients with CKD.
Topics: Humans; Vitamins; Renal Insufficiency, Chronic; Dietary Supplements; Diet; Vitamin K; Vitamin A; Water
PubMed: 36182060
DOI: 10.1053/j.jrn.2022.09.008 -
Journal of Experimental & Clinical... Aug 2023Acute myeloid leukemia (AML) patients bearing the ITD mutation in the tyrosine kinase receptor FLT3 (FLT3-ITD) present a poor prognosis and a high risk of relapse....
BACKGROUND
Acute myeloid leukemia (AML) patients bearing the ITD mutation in the tyrosine kinase receptor FLT3 (FLT3-ITD) present a poor prognosis and a high risk of relapse. FLT3-ITD is retained in the endoplasmic reticulum (ER) and generates intrinsic proteotoxic stress. We devised a strategy based on proteotoxic stress, generated by the combination of low doses of the differentiating agent retinoic acid (R), the proteasome inhibitor bortezomib (B), and the oxidative stress inducer arsenic trioxide (A).
METHODS
We treated FLT3-ITD AML cells with low doses of the aforementioned drugs, used alone or in combinations and we investigated the induction of ER and oxidative stress. We then performed the same experiments in an in vitro co-culture system of FLT3-ITD AML cells and bone marrow stromal cells (BMSCs) to assess the protective role of the niche on AML blasts. Eventually, we tested the combination of drugs in an orthotopic murine model of human AML.
RESULTS
The combination RBA exerts strong cytotoxic activity on FLT3-ITD AML cell lines and primary blasts isolated from patients, due to ER homeostasis imbalance and generation of oxidative stress. AML cells become completely resistant to the combination RBA when treated in co-culture with BMSCs. Nonetheless, we could overcome such protective effects by using high doses of ascorbic acid (Vitamin C) as an adjuvant. Importantly, the combination RBA plus ascorbic acid significantly prolongs the life span of a murine model of human FLT3-ITD AML without toxic effects. Furthermore, we show for the first time that the cross-talk between AML and BMSCs upon treatment involves disruption of the actin cytoskeleton and the actin cap, increased thickness of the nuclei, and relocalization of the transcriptional co-regulator YAP in the cytosol of the BMSCs.
CONCLUSIONS
Our findings strengthen our previous work indicating induction of proteotoxic stress as a possible strategy in FLT3-ITD AML therapy and open to the possibility of identifying new therapeutic targets in the crosstalk between AML and BMSCs, involving mechanotransduction and YAP signaling.
Topics: Humans; Animals; Mice; Tretinoin; Cytoprotection; Disease Models, Animal; Mechanotransduction, Cellular; Proteotoxic Stress; Ascorbic Acid; Cell Death
PubMed: 37653435
DOI: 10.1186/s13046-023-02793-z