scholarly journals Modulation of Intestinal Immune and Barrier Functions by Vitamin A: Implications for Current Understanding of Malnutrition and Enteric Infections in Children

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1128 ◽  
Author(s):  
Pedro de Medeiros ◽  
Daniel Pinto ◽  
Juliana de Almeida ◽  
Juliana Rêgo ◽  
Francisco Rodrigues ◽  
...  
Keyword(s):  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Intestinal Barrier ◽  
Barrier Functions ◽  
Vitamin A Status ◽  
Enteric Infections ◽  
Underlying Mechanisms ◽  
And Function

The micronutrient vitamin A refers to a group of compounds with pleiotropic effects on human health. These molecules can modulate biological functions, including development, vision, and regulation of the intestinal barrier. The consequences of vitamin A deficiency and supplementation in children from developing countries have been explored for several years. These children live in an environment that is highly contaminated by enteropathogens, which can, in turn, influence vitamin A status. Vitamin A has been described to modulate gene expression, differentiation and function of diverse immune cells; however, the underlying mechanisms are not fully elucidated. This review aims to summarize the most updated advances on elucidating the vitamin A effects targeting intestinal immune and barrier functions, which may help in further understanding the burdens of malnutrition and enteric infections in children. Specifically, by covering both clinical and in vivo/in vitro data, we describe the effects of vitamin A related to gut immune tolerance/homeostasis, intestinal barrier integrity, and responses to enteropathogens in the context of the environmental enteric dysfunction. Some of the gaps in the literature that require further research are also highlighted.

In vivo and in vitro Study of the Effects of Vitamin A Deficiency on Rat Third Molar Development

1986 ◽  
Vol 65 (12) ◽  
pp. 1445-1448 ◽  
Author(s):  
S.S. Harris ◽  
J.M. Navia
Keyword(s):  
Vitamin A ◽  
Organ Culture ◽  
Culture System ◽  
Vitamin A Deficiency ◽  
Third Molar ◽  
In Vitro Study ◽  
Organ Culture System ◽  
Vitamin A Status

We have examined the effect of in vivo vitamin A status on subsequent rat third molar formation and mineralization in an in vitro organ culture system. Vitamin A deficiency imposed during an eight-day in vitro period caused effects very similar to those of vitamin A deficiency imposed on rats in vivo. Analysis of the data also demonstrates that retinoic acid is capable of reversing the interference in mineralization of third molars induced by vitamin A deficiency in the organ culture system.

scholarly journals Vitamin A and the biosynthesis of sulphated mucopolysaccharides. Experiments with rats and cultured neoplastic mast cells

1969 ◽  
Vol 111 (4) ◽  
pp. 407-412 ◽  
Author(s):  
D. B. Thomas ◽  
C A Pasternak
Keyword(s):  
Growth Rate ◽  
Mast Cells ◽  
Vitamin A ◽  
Uronic Acid ◽  
Vitamin A Deficiency ◽  
Horse Serum ◽  
Vitamin A Status ◽  
Uronic Acid Content

1. The uptake and incorporation of [35S]sulphate into mucopolysaccharides by colon and duodenum in vitro are unaffected by the vitamin A status of the animals. 2. Uptake and incorporation in vivo are unaffected at 4hr. after injection of [35S]sulphate, but at later times are decreased in some tissues of vitamin A-deficient animals. 3. The rate of removal of 35S from blood, its rate of appearance in urine, the plasma concentration of sulphate and the uronic acid content of several tissues are not significantly altered in vitamin A deficiency. 4. These results, and direct measurement of 35S in mucopolysaccharides at various times after injection of [35S]sulphate, suggest that the synthesis of mucopolysaccharides is unaffected but that their turnover is increased in vitamin A deficiency. 5. Neither the growth rate of, nor the incorporation of [35S]sulphate into heparin by, P815Y and HC cultured neoplastic mast cells is decreased when the horse serum necessary for growth is treated with ultraviolet light or is replaced by serum from vitamin A-deficient rats. 6. The addition of citral is no more toxic to growth rate or to incorporation of 35S than is the addition of vitamin A itself. 7. It is concluded that neoplastic mast cells in culture do not require vitamin A for growth or for the synthesis of heparin. 8. None of these results is compatible with the view that vitamin A or a derivative is directly involved in the biosynthesis of sulphated mucopolysaccharides.

scholarly journals Cellular basis of urothelial squamous metaplasia

2005 ◽  
Vol 171 (5) ◽  
pp. 835-844 ◽  
Author(s):  
Feng-Xia Liang ◽  
Maarten C. Bosland ◽  
Hongying Huang ◽  
Rok Romih ◽  
Solange Baptiste ◽  
...  
Keyword(s):  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Squamous Metaplasia ◽  
Culture Conditions ◽  
Growth Potential ◽  
Basal Cells ◽  
Cellular Basis ◽  
Proximal Urethra

Although the epithelial lining of much of the mammalian urinary tract is known simply as the urothelium, this epithelium can be divided into at least three lineages of renal pelvis/ureter, bladder/trigone, and proximal urethra based on their embryonic origin, uroplakin content, keratin expression pattern, in vitro growth potential, and propensity to keratinize during vitamin A deficiency. Moreover, these cells remain phenotypically distinct even after they have been serially passaged under identical culture conditions, thus ruling out local mesenchymal influence as the sole cause of their in vivo differences. During vitamin A deficiency, mouse urothelium form multiple keratinized foci in proximal urethra probably originating from scattered K14-positive basal cells, and the keratinized epithelium expands horizontally to replace the surrounding normal urothelium. These data suggest that the urothelium consists of multiple cell lineages, that trigone urothelium is closely related to the urothelium covering the rest of the bladder, and that lineage heterogeneity coupled with cell migration/replacement form the cellular basis for urothelial squamous metaplasia.

Vitamin A Status and Hepatic Drug Metabolism in the Rat

1973 ◽  
Vol 51 (1) ◽  
pp. 6-11 ◽  
Author(s):  
G. C. Becking
Keyword(s):  
Vitamin A ◽  
Drug Metabolism ◽  
Vitamin A Deficiency ◽  
Hepatic Drug Metabolism ◽  
Deficient Diet ◽  
Hepatic Drug ◽  
Vitamin A Status ◽  
Cytochrome P 450 ◽  
Liver Vitamin

The effect of vitamin A status on hepatic drug metabolism was studied in rats. Animals were fed diets with and without vitamin A for 20 and 25 days. Weight gains of control and deficient animals were not significantly different, whereas liver vitamin A levels had decreased to less than 10% of control animals after 20 days and were essentially zero after eating the deficient diet for 25 days. Aniline metabolism in vitro and aminopyrine metabolism in vitro and in vivo were significantly lower in male weanling rats fed a vitamin A deficient diet for 20 days. No alteration in in vitro p-nitrobenzoic acid metabolism was noted after 25 days on the test. Vitamin A deficiency did not alter microsomal protein levels or cytochrome c reductase activity but deficient animals did have a lower microsomal cytochrome P-450 content. Hepatic enzyme activities and cytochrome P-450 levels were restored to values approaching those found in control animals by feeding vitamin A deficient rats the vitamin A containing diet for 21 days. Liver vitamin A levels were markedly increased after re-feeding studies but were still significantly lower than control animals.

scholarly journals Plants-Derived Neuroprotective Agents: Cutting the Cycle of Cell Death through Multiple Mechanisms

2017 ◽  
Vol 2017 ◽  
pp. 1-27 ◽  
Author(s):  
Taiwo Olayemi Elufioye ◽  
Tomayo Ireti Berida ◽  
Solomon Habtemariam
Keyword(s):  
Mechanisms Of Action ◽  
Neuroprotective Agents ◽  
Structural Class ◽  
Molecular Features ◽  
Amyotropic Lateral Sclerosis ◽  
Underlying Mechanisms ◽  
And Function ◽  
Lateral Sclerosis

Neuroprotection is the preservation of the structure and function of neurons from insults arising from cellular injuries induced by a variety of agents or neurodegenerative diseases (NDs). The various NDs including Alzheimer’s, Parkinson’s, and Huntington’s diseases as well as amyotropic lateral sclerosis affect millions of people around the world with the main risk factor being advancing age. Each of these diseases affects specific neurons and/or regions in the brain and involves characteristic pathological and molecular features. Hence, several in vitro and in vivo study models specific to each disease have been employed to study NDs with the aim of understanding their underlying mechanisms and identifying new therapeutic strategies. Of the most prevalent drug development efforts employed in the past few decades, mechanisms implicated in the accumulation of protein-based deposits, oxidative stress, neuroinflammation, and certain neurotransmitter deficits such as acetylcholine and dopamine have been scrutinized in great detail. In this review, we presented classical examples of plant-derived neuroprotective agents by highlighting their structural class and specific mechanisms of action. Many of these natural products that have shown therapeutic efficacies appear to be working through the above-mentioned key multiple mechanisms of action.

SNHG5 inhibits the progression of EMT through the ubiquitin-degradation of MTA2 in oesophageal cancer

2020 ◽  
Author(s):  
Sisi Wei ◽  
Shiping Sun ◽  
Xinliang Zhou ◽  
Cong Zhang ◽  
Xiaoya Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Underlying Mechanisms ◽  
And Function

Abstract A substantial fraction of transcripts are known as long noncoding RNAs (lncRNAs), and these transcripts play pivotal roles in the development of cancer. However, little information has been published regarding the functions of lncRNAs in oesophageal squamous cell carcinoma (ESCC) and the underlying mechanisms. In our previous studies, we demonstrated that small nucleolar RNA host gene 5 (SNHG5), a known lncRNA, is dysregulated in gastric cancer (GC). In this study, we explored the expression and function of SNHG5 in development of ESCC. SNHG5 was found to be downregulated in human ESCC tissues and cell lines, and this downregulation was associated with cancer progression, clinical outcomes and survival rates of ESCC patients. Furthermore, we also found that overexpression of SNHG5 significantly inhibited the proliferation, migration and invasion of ESCC cells in vivo and in vitro. Notably, we found that metastasis-associated protein 2 (MTA2) was pulled down by SNHG5 in ESCC cells using RNA pulldown assay. We also found that SNHG5 reversed the epithelial–mesenchymal transition by interacting with MTA2. In addition, overexpression of SNHG5 downregulated the transcription of MTA2 and caused its ubiquitin-mediated degradation. Thus, overexpression of MTA2 partially abrogated the effect of SNHG5 in ESCC cell lines. Furthermore, we found that MTA2 mRNA expression was significantly elevated in ESCC specimens, and a negative correlation between SNHG5 and MTA2 expression was detected. Overall, this study demonstrated, for the first time, that SNHG5-regulated MTA2 functions as an important player in the progression of ESCC and provide a new potential therapeutic strategy for ESCC.

scholarly journals Hyperthermia induces injury to the intestinal mucosa in the mouse: evidence for an oxidative stress mechanism

2012 ◽  
Vol 302 (7) ◽  
pp. R845-R853 ◽  
Author(s):  
S. R. Oliver ◽  
N. A. Phillips ◽  
V. L. Novosad ◽  
M. P. Bakos ◽  
E. E. Talbert ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Oxidation ◽  
Intestinal Barrier ◽  
Epithelial Lining ◽  
Barrier Dysfunction ◽  
Histological Evidence ◽  
Histological Damage ◽  
Underlying Mechanisms

Loss of the intestinal barrier is critical to the clinical course of heat illness, but the underlying mechanisms are still poorly understood. We tested the hypothesis that conditions characteristic of mild heatstroke in mice are associated with injury to the epithelial lining of the intestinal tract and comprise a critical component of barrier dysfunction. Anesthetized mice were gavaged with 4 kDa FITC-dextran (FD-4) and exposed to increasing core temperatures, briefly reaching 42.4°C, followed by 30 min recovery. Arterial samples were collected to measure FD-4 concentration in plasma (in vivo gastrointestinal permeability). The small intestines were then removed to measure histological evidence of injury. Hyperthermia resulted in a ≈2.5-fold elevation in plasma FD-4 and was always associated with significant histological evidence of injury to the epithelial lining compared with matched controls, particularly in the duodenum. When isolated intestinal segments from control animals were exposed to ≥41.5°C, marked increases in permeability were observed within 60 min. These changes were associated with release of lactate dehydrogenase, evidence of protein oxidation via carbonyl formation and histological damage. Coincubation with N-acetylcysteine protected in vitro permeability during hyperthermia and reduced histological damage and protein oxidation. Chelation of intracellular Ca2+ to block tight junction opening during 41.5°C exposure failed to reduce the permeability of in vitro segments. The results demonstrate that hyperthermia exposure in mouse intestine, at temperatures at or below those necessary to induce mild heatstroke, cause rapid and substantial injury to the intestinal lining that may be attributed, in part, to oxidative stress.

scholarly journals Duodenum Intestine-Chip for preclinical drug assessment in a human relevant model

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Magdalena Kasendra ◽  
Raymond Luc ◽  
Jianyi Yin ◽  
Dimitris V Manatakis ◽  
Gauri Kulkarni ◽  
...  
Keyword(s):  
Drug Transport ◽  
Intestinal Barrier ◽  
New Drugs ◽  
Intestinal Barrier Function ◽  
Human Pharmacokinetics ◽  
Relevant Model ◽  
Cell Subpopulations ◽  
And Function

Induction of intestinal drug metabolizing enzymes can complicate the development of new drugs, owing to the potential to cause drug-drug interactions (DDIs) leading to changes in pharmacokinetics, safety and efficacy. The development of a human-relevant model of the adult intestine that accurately predicts CYP450 induction could help address this challenge as species differences preclude extrapolation from animals. Here, we combined organoids and Organs-on-Chips technology to create a human Duodenum Intestine-Chip that emulates intestinal tissue architecture and functions, that are relevant for the study of drug transport, metabolism, and DDI. Duodenum Intestine-Chip demonstrates the polarized cell architecture, intestinal barrier function, presence of specialized cell subpopulations, and in vivo relevant expression, localization, and function of major intestinal drug transporters. Notably, in comparison to Caco-2, it displays improved CYP3A4 expression and induction capability. This model could enable improved in vitro to in vivo extrapolation for better predictions of human pharmacokinetics and risk of DDIs.

scholarly journals Vitamin A-Deficient Hosts Become Nonsymptomatic Reservoirs of Escherichia coli-Like Enteric Infections

2015 ◽  
Vol 83 (7) ◽  
pp. 2984-2991 ◽  
Author(s):  
Kaitlin L. McDaniel ◽  
Katherine H. Restori ◽  
Jeffery W. Dodds ◽  
Mary J. Kennett ◽  
A. Catharine Ross ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Health Concern ◽  
Content Type ◽  
Susceptibility To Infection ◽  
Vitamin A Status ◽  
Enteric Infections ◽  
Systemic Cytokine Production ◽  
Susceptible Populations

Vitamin A deficiency (A−) remains a public health concern in developing countries and is associated with increased susceptibility to infection.Citrobacter rodentiumwas used to model humanEscherichia coliinfections. A−mice developed a severe and lethal (40%) infection. Vitamin A-sufficient (A+) mice survived and cleared the infection by day 25. Retinoic acid treatment of A−mice at the peak of the infection eliminatedC. rodentiumwithin 16 days. Inflammation levels were not different between A+and A−mouse colons, although the A−mice were still infected at day 37. Increased mortality of A−mice was not due to systemic cytokine production, an inability to clear systemicC. rodentium, or increased pathogenicity. Instead, A−mice developed a severe gut infection with most of the A−mice surviving and resolving inflammation but not eliminating the infection. Improvements in vitamin A status might decrease susceptibility to enteric pathogens and prevent potential carriers from spreading infection to susceptible populations.

scholarly journals Impaired T lymphocyte immune response in vitamin A depleted rats and chicks

1989 ◽  
Vol 62 (2) ◽  
pp. 439-449 ◽  
Author(s):  
Aharon Friedman ◽  
David Sklan
Keyword(s):  
Immune Response ◽  
Vitamin A ◽  
Immune Responses ◽  
T Lymphocyte ◽  
Vitamin A Deficiency ◽  
Retinyl Acetate ◽  
Vitamin A Status ◽  
Severe Impairment ◽  
Lymphocyte Activity

Vitamin A deficiency results in decreased immune responses; the objective of the present study was to investigate the involvement of T lymphocytes in the depression of immune responses resulting from vitamin A depletion. This objective was achieved by evaluating antigen-specific T lymphocyte proliferative responses in vitro as vitamin A depletion developed. The evaluation was performed in both rat and chick to examine the generality of immune effects due to vitamin A depletion. Our findings show that vitamin A depletion led to severe impairment of T lymphocyte activity in both animal models, and that this was directly related to the vitamin A status in both species. Immune response impairment was found to precede other manifestations of vitamin A deficiency, and was rapidly corrected by feeding retinyl acetate boluses. This implied a possible regulatory, rather than constitutive, role of vitamin A in immune responsiveness.

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