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RNA regulons are essential in intestinal homeostasis.
Parham, LR, Williams, PA, Chatterji, P, Whelan, KA, Hamilton, KE
American journal of physiology. Gastrointestinal and liver physiology. 2019;(1):G197-G204
Abstract
Intestinal epithelial cells are among the most rapidly proliferating cell types in the human body. There are several different subtypes of epithelial cells, each with unique functional roles in responding to the ever-changing environment. The epithelium's ability for rapid and customized responses to environmental changes requires multitiered levels of gene regulation. An emerging paradigm in gastrointestinal epithelial cells is the regulation of functionally related mRNA families, or regulons, via RNA-binding proteins (RBPs). RBPs represent a rapid and efficient mechanism to regulate gene expression and cell function. In this review, we will provide an overview of intestinal epithelial RBPs and how they contribute specifically to intestinal epithelial stem cell dynamics. In addition, we will highlight key gaps in knowledge in the global understanding of RBPs in gastrointestinal physiology as an opportunity for future studies.
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Metal ligands in micronutrient acquisition and homeostasis.
Clemens, S
Plant, cell & environment. 2019;(10):2902-2912
Abstract
Acquisition and homeostasis of micronutrients such as iron (Fe) and zinc (Zn) pose specific challenges. Poor solubility and high reactivity require controlled synthesis and supply of ligands to complex these metals extracellularly and intracellularly. Cytosolic labile pools represent only a minute fraction of the total cellular content. Several low-molecular-weight ligands are known in plants, including sulfur ligands (cysteine and peptides), nitrogen/oxygen ligands (S-adenosyl-l-methionine-derived molecules and histidine), and oxygen ligands (phenolics and organic acids). Some ligands are secreted into the extracellular space and influence the phytoavailability of metal ions. A second principal function is the intracellular buffering of micronutrients as well as the facilitation of long-distance transport in xylem and phloem. Furthermore, low-molecular-weight ligands are involved in the storage of metals, predominantly in vacuoles. A detailed molecular understanding is hampered by technical limitations, in particular the difficulty to detect and quantify cellular metal-ligand complexes. More, but still too little, is known about ligand synthesis and the transport across membranes, either with or without a complexed metal. Metal ligands have an immediate impact on human well-being. Engineering metal ligand synthesis and distribution in crops has tremendous potential to improve the nutritional quality of food and to tackle major human health risks.
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Homeostatic and neurocognitive control of energy intake in response to exercise in pediatric obesity: a psychobiological framework.
Thivel, D, Finlayson, G, Blundell, JE
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2019;(2):316-324
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Abstract
While energy intake and energy expenditure have long been studied independently, the alarming progression of obesity has led to a more integrative approach to energy balance considering their potential interactions. Although the available literature concerned with the effect of chronic and acute exercise on energy intake and appetite control in adults is considerable, these questions remain less explored among children and adolescents. Based on the search of four databases (Medline, Embase, PsycINFO and Cochrane Library; articles published until May 2018), the objective of this review is to summarize and discuss the effect of acute and chronic physical exercise on energy intake and appetite control in children and adolescents with obesity, and to identify the physiological and neurocognitive signals and pathways involved. Evidence suggested that acute intensive exercise has the potential to reduce subsequent energy intake in children and adolescents with obesity but not healthy weight, through both peripheral (mainly gastro-peptides) and neurocognitive (neural responses to food cues) pathways. The nutritional responses to chronic physical activity remain less clear and require further consideration, especially from an anti-obesity perspective.
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The potential application of genome editing by using CRISPR/Cas9, and its engineered and ortholog variants for studying the transcription factors involved in the maintenance of phosphate homeostasis in model plants.
Jyoti, A, Kaushik, S, Srivastava, VK, Datta, M, Kumar, S, Yugandhar, P, Kothari, SL, Rai, V, Jain, A
Seminars in cell & developmental biology. 2019;:77-90
Abstract
Phosphorus (P), an essential macronutrient, is pivotal for growth and development of plants. Availability of phosphate (Pi), the only assimilable P, is often suboptimal in rhizospheres. Pi deficiency triggers an array of spatiotemporal adaptive responses including the differential regulation of several transcription factors (TFs). Studies on MYB TF PHR1 in Arabidopsis thaliana (Arabidopsis) and its orthologs OsPHRs in Oryza sativa (rice) have provided empirical evidence of their significant roles in the maintenance of Pi homeostasis. Since the functional characterization of PHR1 in 2001, several other TFs have now been identified in these model plants. This raised a pertinent question whether there are any likely interactions across these TFs. Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has provided an attractive paradigm for editing genome in plants. Here, we review the applications and challenges of this technique for genome editing of the TFs for deciphering the function and plausible interactions across them. This technology could thus provide a much-needed fillip towards engineering TFs for generating Pi use efficient plants for sustainable agriculture. Furthermore, we contemplate whether this technology could be a viable alternative to the controversial genetically modified (GM) rice or it may also eventually embroil into a limbo.
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Nutritional Modulation of Immune and Central Nervous System Homeostasis: The Role of Diet in Development of Neuroinflammation and Neurological Disease.
Estrada, JA, Contreras, I
Nutrients. 2019;(5)
Abstract
The gut-microbiome-brain axis is now recognized as an essential part in the regulation of systemic metabolism and homeostasis. Accumulating evidence has demonstrated that dietary patterns can influence the development of metabolic alterations and inflammation through the effects of nutrients on a multitude of variables, including microbiome composition, release of microbial products, gastrointestinal signaling molecules, and neurotransmitters. These signaling molecules are, in turn, implicated in the regulation of the immune system, either promoting or inhibiting the production of pro-inflammatory cytokines and the expansion of specific leukocyte subpopulations, such as Th17 and Treg cells, which are relevant in the development of neuroinflammatory and neurodegenerative conditions. Metabolic diseases, like obesity and type 2 diabetes mellitus, are related to inadequate dietary patterns and promote variations in the aforementioned signaling pathways in patients with these conditions, which have been linked to alterations in neurological functions and mental health. Thus, maintenance of adequate dietary patterns should be an essential component of any strategy aiming to prevent neurological pathologies derived from systemic metabolic alterations. The present review summarizes current knowledge on the role of nutrition in the modulation of the immune system and its impact in the development of neuroinflammation and neurological disease.
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6.
Targeting cellular cholesterol for anticancer therapy.
Gu, L, Saha, ST, Thomas, J, Kaur, M
The FEBS journal. 2019;(21):4192-4208
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Abstract
Cholesterol dyshomeostasis in cancer cells leads to intracellular cholesterol accumulation, which imparts drug resistance and allows these cells to evade apoptotic signalling processes and maintain continuous cell division and proliferation. Therefore, cholesterol lowering in cancer cells has been envisaged as a potential anticancer strategy. In this direction, two therapeutic strategies have been proposed: (a) to inhibit the biosynthesis of cholesterol in the cells and (b) to deplete excess cholesterol from cancer cells. In the first phase of this review, we collate the cancer signalling pathways (particularly in breast cancer) that are perturbed by cholesterol dyshomeostasis and highlight recent drug discovery efforts to develop cholesterol-lowering compounds, some of which are currently under clinical trials. In the second phase, based on the analysis of the available scientific evidence, we conceptualize and argue that the depletion of excess cholesterol could sensitize cancer cells to available therapeutics and may also help to alleviate cancer drug resistance.
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Physiology of energy homeostasis: Models, actors, challenges and the glucoadipostatic loop.
Chapelot, D, Charlot, K
Metabolism: clinical and experimental. 2019;:11-25
Abstract
The aim of this review is to discuss the physiology of energy homeostasis (EH), which is a debated concept. Thus, we will see that the set-point theory is highly challenged and that other models integrating an anticipative component, such as energy allostasis, seem more relevant to experimental reports and life preservation. Moreover, the current obesity epidemic suggests that EH is poorly efficient in the modern human dietary environment. Non-homeostatic phenomena linked to hedonism and reward seem to profoundly impair EH. In this review, the apparent failed homeostatic responses to energy challenges such as exercise, cafeteria diet, overfeeding and diet-induced weight loss, as well as their putative determinants, are analyzed to highlight the mechanisms of EH. Then, the hormonal, neuronal, and metabolic factors of energy intake or energy expenditure are briefly presented. Last, this review focuses on the contributions of two of the most pivotal and often overlooked determinants of EH: the availability of endogenous energy and the pattern of energy intake. A glucoadipostatic loop model is finally proposed to link energy stored in adipose tissue to EH through changes in eating behavior via leptin and sympathetic nervous system activity.
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Redox homeostasis in sport: do athletes really need antioxidant support?
Antonioni, A, Fantini, C, Dimauro, I, Caporossi, D
Research in sports medicine (Print). 2019;(2):147-165
Abstract
Supplementation with antioxidants received interest as suitable tool for preventing or reducing exercise-related oxidative stress possibly leading to improvement of sport performance in athletes. To date, it is difficult to reach a conclusion on the relevance of antioxidants supplementation in athletes and/or well-trained people. The general picture that emerges from the available data indicates that antioxidants requirement can be covered by dosage equal or close to the recommended dietary allowance (RDA) provided by consumption of a balanced, well-diversified diet. Nevertheless, it remains open the possibility that in specific context, such as in sports characterized by high intensity and/or exhaustive regimes, supplementation with antioxidants could be appropriated to avoid or reduce the damaging effect of these type of exercise. This review will discuss the findings of a number of key studies on the advantages and/or disadvantages for athletes of using antioxidants supplementation, either individually or in combination.
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Copper homeostasis as target of both consolidated and innovative strategies of anti-tumor therapy.
De Luca, A, Barile, A, Arciello, M, Rossi, L
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2019;:204-213
Abstract
BACKGROUND Copper was reported to be involved in the onset and progression of cancer. Proteins in charge of copper uptake and distribution, as well as cuproenzymes, are altered in cancer. More recently, proteins involved in signaling cascades, regulating cell proliferation, and anti-apoptotic protein factors were found to interact with copper. Therefore, therapeutic strategies using copper complexing molecules have been proposed for cancer therapy and used in clinical trials. OBJECTIVES This review will focus on novel findings about the involvement of copper and cupro-proteins in cancer dissemination process, epithelium to mesenchymal transition and vascularization. Particularly, implication of well-established (e.g. lysil oxidase) or newly identified copper-binding proteins (e.g. MEMO1), as well as their interplay, will be discussed. Moreover, we will describe recently synthesized copper complexes, including plant-derived ones, and their efficacy in contrasting cancer development. CONCLUSIONS The research on the involvement of copper in cancer is still an open field. Further investigation is required to unveil the mechanisms involved in copper delivery to the novel copper-binding proteins, which may identify other possible gene and protein targets for cancer therapy.
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Amino acids and amino acid sensing: implication for aging and diseases.
Dato, S, Hoxha, E, Crocco, P, Iannone, F, Passarino, G, Rose, G
Biogerontology. 2019;(1):17-31
Abstract
Biogerontological research indicates nutrition as one of the major determinants of healthy aging, due to the role of nutrients in maintaining the dynamic-homeostasis of the organism. In this frame, the importance of proteins and constitutive amino acids (AAs), and in particular of functional AAs is emerging. The ability to sense and respond to changes in AAs availability is mediated by a complex network of dynamic players, crucial for an efficient regulation of their downstream effects. Here, we reviewed the current knowledge about the involvement of AA sensing mechanisms in aging and age-related diseases, focusing our attention on mTORC1 and AA transporters. In this context it is of note that alterations in AA sensors have been reported to be directly implicated in age-related phenotypes, suggesting that their modulation can represent a possible strategy for modulating (and possibly delaying) aging decline. Furthermore, these alterations may influence the effects of AA supplementation, by influencing the individual answer to AA availability. On the whole, evidences support the hypothesis that the efficiency of components of AA sensing network may have important implications for therapy, and their knowledge may be crucial for programming AA supplementation for contrasting age-related phenotypes, opening new opportunities for therapeutic interventions aimed to promote human health span.