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Retinoic acid drives intestine-specific adaptation of effector ILC2s originating from distant sites.The Journal of Experimental Medicine Dec 2023Adaptation of immune cells to tissue-specific microenvironments is a crucial process in homeostasis and inflammation. Here, we show that murine effector type 2 innate...
Adaptation of immune cells to tissue-specific microenvironments is a crucial process in homeostasis and inflammation. Here, we show that murine effector type 2 innate lymphoid cells (ILC2s) from various organs are equally effective in repopulating ILC2 niches in other anatomical locations where they adapt tissue-specific phenotypes of target organs. Single-cell transcriptomics of ILC2 populations revealed upregulation of retinoic acid (RA) signaling in ILC2s during adaptation to the small intestinal microenvironment, and RA signaling mediated reprogramming of kidney effector ILC2s toward the small intestinal phenotype in vitro and in vivo. Inhibition of intestinal ILC2 adaptation by blocking RA signaling impaired worm expulsion during Strongyloides ratti infection, indicating functional importance of ILC2 tissue imprinting. In conclusion, this study highlights that effector ILC2s retain the ability to adapt to changing tissue-specific microenvironments, enabling them to exert tissue-specific functions, such as promoting control of intestinal helminth infections.
Topics: Mice; Animals; Immunity, Innate; Tretinoin; Lymphocytes; Intestines; Inflammation; Cytokines
PubMed: 37773047
DOI: 10.1084/jem.20221015 -
Nutrients Nov 2023The new coronavirus infection represents a serious threat to global health and economies. In this sense, it is paramount to know the nutritional factors that may be...
The new coronavirus infection represents a serious threat to global health and economies. In this sense, it is paramount to know the nutritional factors that may be related to the prognosis of the disease. Evidence shows that vitamin A may play an important preventive and therapeutic role in supporting respiratory infections as in COVID-19. The aim of our study was to evaluate the association of vitamin A (retinol) status with the prognosis of the disease. A case-control study from a cohort study was conducted in Brazil between May and October 2020. The study population was chosen by convenience, consisting of participants diagnosed with COVID-19. Recruitment was carried out using different approaches, including through dissemination on social media and in four hospitals in the city of Natal/RN, Brazil, recruiting participants from the COVID-19 ward and hospitalized participants who tested positive for the disease. The participants were allocated into two groups according to severity, with a group of mild ( = 88) or critical ( = 106) patients and compared to a control group (selected before the pandemic, = 46). The extraction of retinol serum was performed and analyzed using the high-performance liquid chromatography method (HPLC). The retinol level was calculated in mmol/L, and levels below 0.7 μmol/L (20 µg/dL) were considered to be a vitamin A deficiency. Our findings suggest that the participants with mild and critical COVID-19 had lower retinol levels compared to the healthy controls ( = 0.03). In addition, milder cases of COVID-19 were associated with increased symptoms and prolonged symptoms after 90 days since the beginning of infection. However, the survival analysis showed no association with higher cases of death among participants with vitamin A deficiency ( = 0.509). More studies are needed to understand how nutritional status, including vitamin A levels, can influence prognosis and is a risk factor for the development of long COVID syndrome.
Topics: Humans; Vitamin A; COVID-19; Vitamin A Deficiency; Case-Control Studies; Cohort Studies; Post-Acute COVID-19 Syndrome
PubMed: 37960295
DOI: 10.3390/nu15214642 -
Advances in Nutrition (Bethesda, Md.) Nov 2023Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases risk of developmental and degenerative diseases, and accelerates aging.... (Review)
Review
Protective Effects of Micronutrient Supplements, Phytochemicals and Phytochemical-Rich Beverages and Foods Against DNA Damage in Humans: A Systematic Review of Randomized Controlled Trials and Prospective Studies.
Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases risk of developmental and degenerative diseases, and accelerates aging. Optimizing nutrient intake can minimize accrual of DNA damage. The objectives of this review are to: 1) assemble and systematically analyze high-level evidence for the effect of supplementation with micronutrients and phytochemicals on baseline levels of DNA damage in humans, and 2) use this knowledge to identify which of these essential micronutrients or nonessential phytochemicals promote DNA integrity in vivo in humans. We conducted systematic literature searches of the PubMed database to identify interventional, prospective, cross-sectional, or in vitro studies that explored the association between nutrients and established biomarkers of DNA damage associated with developmental and degenerative disease risk. Biomarkers included lymphocyte chromosome aberrations, lymphocyte and buccal cell micronuclei, DNA methylation, lymphocyte/leukocyte DNA strand breaks, DNA oxidation, telomere length, telomerase activity, and mitochondrial DNA mutations. Only randomized, controlled interventions and uncontrolled longitudinal intervention studies conducted in humans were selected for evaluation and data extraction. These studies were ranked for the quality of their study design. In all, 96 of the 124 articles identified reported studies that achieved a quality assessment score ≥ 5 (from a maximum score of 7) and were included in the final review. Based on these studies, nutrients associated with protective effects included vitamin A and its precursor β-carotene, vitamins C, E, B1, B12, folate, minerals selenium and zinc, and phytochemicals such as curcumin (with piperine), lycopene, and proanthocyanidins. These findings highlight the importance of nutrients involved in (i) DNA metabolism and repair (folate, vitamin B, and zinc) and (ii) prevention of oxidative stress and inflammation (vitamins A, C, E, lycopene, curcumin, proanthocyanidins, selenium, and zinc). Supplementation with certain micronutrients and their combinations may reduce DNA damage and promote cellular health by improving the maintenance of genome integrity.
Topics: Humans; Prospective Studies; Selenium; Lycopene; Cross-Sectional Studies; Curcumin; Proanthocyanidins; Randomized Controlled Trials as Topic; Vitamins; Vitamin A; Micronutrients; Folic Acid; Zinc; Beverages; Phytochemicals; DNA; DNA Damage; Biomarkers; Dietary Supplements
PubMed: 37573943
DOI: 10.1016/j.advnut.2023.08.004 -
Pharmacological Reports : PR Oct 2023Disruption of the skin barrier and immunity has been associated with several skin diseases, namely atopic dermatitis (AD), psoriasis, and acne. Resident and non-resident... (Review)
Review
Disruption of the skin barrier and immunity has been associated with several skin diseases, namely atopic dermatitis (AD), psoriasis, and acne. Resident and non-resident immune cells and the barrier system of the skin are integral to innate immunity. Recent advances in understanding skin microbiota have opened the scope of further understanding the various communications between these microbiota and skin immune cells. Vitamins, being one of the important micronutrients, have been reported to exert antioxidant, anti-inflammatory, and anti-microbial effects. The immunomodulatory action of vitamins can halt the progression of skin diseases, and thus, understanding the immuno-pharmacology of these vitamins, especially for skin diseases can pave the way for their therapeutic potential. At the same time, molecular and cellular markers modulated with these vitamins and their derivatives need to be explored. The present review is focused on significant vitamins (vitamins A, B3, C, D, and E) consumed as nutritional supplements to discuss the outcomes and scope of studies related to skin immunity, health, and diseases.
Topics: Humans; Vitamins; Skin; Dermatitis, Atopic; Microbiota; Immunity, Innate; Vitamin A; Vitamin K
PubMed: 37673852
DOI: 10.1007/s43440-023-00520-1 -
Journal of Health, Population, and... Jan 2024A healthy diet play an important role in the prevention and even treatment of various diseases. Proper nutrition plays an important role in boosting of immune system.... (Review)
Review
BACKGROUND AND AIMS
A healthy diet play an important role in the prevention and even treatment of various diseases. Proper nutrition plays an important role in boosting of immune system. These include the consumption of macronutrients such as proteins, lipids, carbohydrates, and also micronutrients including vitamins. Here, we aimed to systematically review the effects of macronutrients and micronutrients on the prevention and treatment of COVID-19.
METHODS
We searched the databases of PubMed, Scopus, Embase, and Web of Science on December 23, 2023. The records were downloaded into an EndNote file, the duplicates were removed, and the studies underwent a two-phase screening process based on their title/abstracts and full texts. The included articles were screened and underwent inclusion and exclusion criteria. We included the English systematic reviews and meta-analyses that concurred with the aim of our study. The selected articles were assessed by Cochrane's Risk of Bias in Systematic Reviews for the quality check. The data of the eligible studies were extracted in a pre-designed word table and were used for the qualitative synthesis.
RESULTS
A total of 28 reviews were included in this study. Most studies have shown that micronutrients are effective in morbidity and mortality controlling in viral respiratory infections such as COVID-19 but some studies have shown that micronutrients are sometimes not effective in controlling severity. On the other hand, calcifediol was by far the most successful agent in reducing intensive care needs and mortality between studies.
CONCLUSION
Individuals without malnutrition had a reduced risk of SARS-CoV-2 infection and severe disease. The administration of Vitamin D is effective in reducing the morbidity and mortality of COVID-19 patients. Patients with vitamin D deficiency were more prone to experience severe infection, and they were at higher risk of morbidities and mortality. Other micronutrients such as Vitamin A, Vitamin B, and Zinc also showed some benefits in patients with COVID-19. Vitamin C showed no efficacy in COVID-19 management even in intravenous form or in high doses.
Topics: Humans; COVID-19; SARS-CoV-2; Systematic Reviews as Topic; Vitamins; Nutrients; Vitamin A; Micronutrients
PubMed: 38287379
DOI: 10.1186/s41043-024-00504-8 -
BMC Pulmonary Medicine Apr 2024The Corona Virus Disease 2019 (COVID-19) pandemic has struck globally. Whether the related proteins of retinoic acid (RA) signaling pathway are causally associated with...
BACKGROUND
The Corona Virus Disease 2019 (COVID-19) pandemic has struck globally. Whether the related proteins of retinoic acid (RA) signaling pathway are causally associated with the risk of COVID-19 remains unestablished. We conducted a two-sample Mendelian randomization (MR) study to assess the associations of retinol, retinol binding protein 4 (RBP4), retinol dehydrogenase 16 (RDH16) and cellular retinoic acid binding protein 1 (CRABP1) with COVID-19 in European population.
METHODS
The outcome utilized the summary statistics of COVID-19 from the COVID-19 Host Genetics Initiative. The exposure data were obtained from public genome wide association study (GWAS) database. We extracted SNPs from exposure data and outcome data. The inverse variance weighted (IVW), MR-Egger and Wald ratio methods were employed to assess the causal relationship between exposure and outcome. Sensitivity analyses were performed to ensure the validity of the results.
RESULTS
The MR estimates showed that retinol was associated with lower COVID-19 susceptibility using IVW (OR: 0.69, 95% CI: 0.53-0.90, P: 0.0065), whereas the associations between retinol and COVID-19 hospitalization or severity were not significant. RBP4 was associated with lower COVID-19 susceptibility using the Wald ratio (OR: 0.83, 95% CI: 0.72-0.95, P: 0.0072). IVW analysis showed RDH16 was associated with increased COVID-19 hospitalization (OR: 1.10, 95% CI: 1.01-1.18, P: 0.0199). CRABP1 was association with lower COVID-19 susceptibility (OR: 0.95, 95% CI: 0.91-0.99, P: 0.0290) using the IVW.
CONCLUSIONS
We found evidence of possible causal association of retinol, RBP4, RDH16 and CRABP1 with the susceptibility, hospitalization and severity of COVID-19. Our study defines that retinol is significantly associated with lower COVID-19 susceptibility, which provides a reference for the prevention of COVID-19 with vitamin A supplementation.
Topics: Humans; COVID-19; Genetic Predisposition to Disease; Genome-Wide Association Study; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Receptors, Retinoic Acid; Retinol-Binding Proteins, Plasma; SARS-CoV-2; Vitamin A
PubMed: 38671384
DOI: 10.1186/s12890-024-03013-w -
Cureus Dec 2023Vitamin A deficiency (VAD) or excess in expectant mothers can result in fetal abnormalities such as night blindness, bone anomalies, or epithelial cell problems. In... (Review)
Review
Vitamin A deficiency (VAD) or excess in expectant mothers can result in fetal abnormalities such as night blindness, bone anomalies, or epithelial cell problems. In contrast, excessive vitamin A in pregnancy can precipitate fetal central nervous system deformities. During pregnancy, a pregnant woman should monitor her vitamin A intake ensuring she gets the recommended dosage, but also ensuring she doesn't exceed the recommended dosage, because either one can result in teratogenicity in the fetus. The widespread and unregulated use of multivitamins and supplements makes consuming doses greater than the recommended quantity more common in developed countries. While vitamin A excess is more common in developed countries, deficiency is most prevalent in developing countries. With proper maintenance, regulation, and education about VAD and excess, a pregnant mother can diminish potential harm to her fetus and potential teratogenic risks.
PubMed: 38226115
DOI: 10.7759/cureus.50513 -
Nutrients Sep 2023Trace elements and vitamins, collectively known as micronutrients, are essential for basic metabolic reactions in the human body. Their deficiency or, on the contrary,... (Review)
Review
Trace elements and vitamins, collectively known as micronutrients, are essential for basic metabolic reactions in the human body. Their deficiency or, on the contrary, an increased amount can lead to serious disorders. Research in recent years has shown that long-term abnormal levels of micronutrients may be involved in the etiopathogenesis of some neurological diseases. Acute and chronic alterations in micronutrient levels may cause other serious complications in neurological diseases. Our aim was to summarize the knowledge about micronutrients in relation to selected neurological diseases and comment on their importance and the possibilities of therapeutic intervention in clinical practice.
Topics: Humans; Micronutrients; Vitamins; Trace Elements; Vitamin A; Nervous System Diseases
PubMed: 37836413
DOI: 10.3390/nu15194129 -
International Journal of Molecular... Nov 2023Diabetes is a serious chronic metabolic disease that causes complications over time, bringing serious public health challenges that affect different countries across the... (Review)
Review
Diabetes is a serious chronic metabolic disease that causes complications over time, bringing serious public health challenges that affect different countries across the world. The current clinical drugs for diabetes may lead to adverse effects such as hypoglycemia and liver and abdominal distension and pain, which prompt people to explore new treatments for diabetes without side effects. The research objective of this review article is to systematically review studies on vitamins and diabetes and to explain their possible mechanism of action, as well as to assess the role of vitamins as drugs for the prevention and treatment of diabetes. To achieve our objective, we searched scientific databases in PubMed Central, Medline databases and Web of Science for articles, using "vitamin" and "diabetes" as key words. The results of numerous scientific investigations revealed that vitamin levels were decreased in humans and animals with diabetes, and vitamins show promise for the prevention and/or control of diabetes through anti-inflammation, antioxidation and the regulation of lipid metabolism. However, a few studies showed that vitamins had no positive effect on the development of diabetes. Currently, studies on vitamins in the treatment of diabetes are still very limited, and there are no clinical data to clarify the dose-effect relationship between vitamins and diabetes; therefore, vitamins are not recommended as routine drugs for the treatment of diabetes. However, we still emphasize the great potential of vitamins in the prevention and treatment of diabetes, and higher quality studies are needed in the future to reveal the role of vitamins in the development of diabetes.
Topics: Humans; Vitamins; Dietary Supplements; Vitamin A; Vitamin K; Diabetes Mellitus
PubMed: 38003557
DOI: 10.3390/ijms242216371 -
EBioMedicine Nov 2023Transient ischemic attack (TIA) induces ischemic tolerance that can reduce the subsequent ischemic damage and improve prognosis of patients with stroke. However, the...
BACKGROUND
Transient ischemic attack (TIA) induces ischemic tolerance that can reduce the subsequent ischemic damage and improve prognosis of patients with stroke. However, the underlying mechanisms remain elusive. Recent advances in plasma metabolomics analysis have made it a powerful tool to investigate human pathophysiological phenotypes and mechanisms of diseases. In this study, we aimed to identify the bioactive metabolites from the plasma of patients with TIA for determination of their prophylactic and therapeutic effects on protection against cerebral ischemic stroke, and the mechanism of TIA-induced ischemic tolerance against subsequent stroke.
METHODS
Metabolomic profiling using liquid chromatography-mass spectrometry was performed to identify the TIA-induced differential bioactive metabolites in the plasma samples of 20 patients at day 1 (time for basal metabolites) and day 7 (time for established chronic ischemic tolerance-associated metabolites) after onset of TIA. Mouse middle cerebral artery occlusion (MCAO)-induced stroke model was used to verify their prophylactic and therapeutic potentials. Transcriptomics changes in circulating neutrophils of patients with TIA were determined by RNA-sequencing. Multivariate statistics and integrative analysis of metabolomics and transcriptomics were performed to elucidate the potential mechanism of TIA-induced ischemic tolerance.
FINDINGS
Plasma metabolomics analysis identified five differentially upregulated metabolites associated with potentially TIA-induced ischemic tolerance, namely all-trans 13,14 dihydroretinol (atDR), 20-carboxyleukotriene B4, prostaglandin B2, cortisol and 9-KODE. They were associated with the metabolic pathways of retinol, arachidonic acid, and neuroactive ligand-receptor interaction. Prophylactic treatment of MCAO mice with these five metabolites significantly improved neurological functions. Additionally, post-stroke treatment with atDR or 9-KODE significantly reduced the cerebral infarct size and enhanced sensorimotor functions, demonstrating the therapeutic potential of these bioactive metabolites. Mechanistically, we found in patients with TIA that these metabolites were positively correlated with circulating neutrophil counts. Integrative analysis of plasma metabolomics and neutrophil transcriptomics further revealed that TIA-induced metabolites are significantly correlated with specific gene expression in circulating neutrophils which showed prominent enrichment in FoxO signaling pathway and upregulation of the anti-inflammatory cytokine IL-10. Finally, we demonstrated that the protective effect of atDR-pretreatment on MCAO mice was abolished when circulating neutrophils were depleted.
INTERPRETATION
TIA-induced potential ischemic tolerance is associated with upregulation of plasma bioactive metabolites which can protect against cerebral ischemic damage and improve neurological functions through a positive role of circulating neutrophils.
FUNDING
National Natural Science Foundation of China (81974210), Science and Technology Planning Project of Guangdong Province, China (2020A0505100045), Natural Science Foundation of Guangdong Province (2019A1515010671), Science and Technology Program of Guangzhou, China (2023A03J0577), and Natural Science Foundation of Jiangxi, China(20224BAB216043).
Topics: Humans; Mice; Animals; Ischemic Attack, Transient; Neutrophils; Stroke; Infarction, Middle Cerebral Artery; Metabolomics
PubMed: 37890369
DOI: 10.1016/j.ebiom.2023.104845