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1.
Effects of Dapagliflozin on Circulating Markers of Phosphate Homeostasis.
de Jong, MA, Petrykiv, SI, Laverman, GD, van Herwaarden, AE, de Zeeuw, D, Bakker, SJL, Heerspink, HJL, de Borst, MH
Clinical journal of the American Society of Nephrology : CJASN. 2019;(1):66-73
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Abstract
BACKGROUND AND OBJECTIVES The sodium glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin is a novel drug for the treatment of diabetes mellitus. Recent studies suggest that SGLT-2 inhibitors affect phosphate homeostasis, but their effects on phosphate-regulating hormones in patients with diabetic kidney disease are still unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a post-hoc analysis of a double-blind, randomized, crossover trial in patients with type 2 diabetes with early-stage diabetic kidney disease on stable renin-angiotensin-aldosterone system blockade, with an albumin-to-creatinine ratio between 100 and 3500 mg/g, eGFR≥45 ml/min per 1.73 m2, and glycosylated hemoglobin≥7.2% and <11.4%. Patients were randomized to dapagliflozin 10 mg/d or placebo during consecutive 6-week study periods, separated by a 6-week wash-out. We investigated effects on circulating phosphate, calcium, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) levels. RESULTS Thirty-one patients (age 62 years; 23% female) were analyzed. Compared with placebo, dapagliflozin increased serum phosphate by 9% (95% confidence interval, 4% to 15%; P=0.002), PTH increased by 16% (3% to 30%; P=0.01), FGF23 increased by 19% (0.3% to 42%; P=0.05), and serum 1,25(OH)2D decreased by -12% (-25% to 4%; P=0.12). Calcium and 25(OH)D were unaffected. We found no correlation between changes in markers of phosphate homeostasis and changes in eGFR or 24-hour albumin excretion during dapagliflozin treatment. CONCLUSIONS Dapagliflozin increases serum phosphate, plasma PTH, and FGF23. This effect was independent of concomitant changes in eGFR or 24-hour albumin excretion.
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Polyphenol-rich curry made with mixed spices and vegetables benefits glucose homeostasis in Chinese males (Polyspice Study): a dose-response randomized controlled crossover trial.
Haldar, S, Chia, SC, Lee, SH, Lim, J, Leow, MK, Chan, ECY, Henry, CJ
European journal of nutrition. 2019;(1):301-313
Abstract
PURPOSE To investigate acute effects of two doses of a polyphenol-rich curry made with seven different spices and four base vegetables, eaten with white rice, on 24 h glucose response, postprandial insulinemia, triglyceridemia and 24 h urinary total polyphenol excretion (TPE). METHODS Randomized, controlled, dose-response crossover trial in healthy, Chinese men [n = 20, mean ± standard deviation (SD) age 23.7 ± 2.30 years, BMI 23.0 ± 2.31 kg/m2] who consumed test meals matched for calories, macronutrients and total vegetables content, consisting either Dose 0 Control (D0C) or Dose 1 Curry (D1C) or Dose 2 Curry (D2C) meal. 24 h glucose concentration was measured using continuous glucose monitoring (CGM), together with postprandial plasma insulin and triglyceride for up to 7 h. Total polyphenol content (TPC) of test meals and urinary TPE were measured using the Folin-Ciocalteu assay. RESULTS TPC for D0C, D1C and D2C were 130 ± 18, 556 ± 19.7 and 1113 ± 211.6 mg gallic acid equivalent (GAE) per portion served, respectively (p < 0.0001). Compared with D0C meal, we found significant linear dose-response reductions in the 3-h postprandial incremental AUC (iAUC) for CGM glucose of 19% and 32% during D1C and D2C meals respectively (p < 0.05) and non-significant linear dose response reductions in iAUC of insulin (p = 0.089). Notably, we found significant dose-dependent increases in postprandial triglyceride with increasing curry doses (p < 0.01). Significant increases in TPE with increasing curry doses were also observed (p < 0.01). CONCLUSION Polyphenol-rich curry intake can improve postprandial glucose homeostasis. The longer term effects remain to be established.
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Magnesium transport and homeostasis-related gene expression in skeletal muscle of young and old adults: analysis of the transcriptomic data from the PROOF cohort Study.
Coudy-Gandilhon, C, Gueugneau, M, Taillandier, D, Combaret, L, Polge, C, Roche, F, Barthélémy, JC, Féasson, L, Maier, JA, Mazur, A, et al
Magnesium research. 2019;(3):72-82
Abstract
Magnesium (Mg2+) is critical for a number of biological processes and 25% body Mg2+ is located in the skeletal muscle. Mg2+ transport and homeostasis systems (MgTHs) regulate intracellular Mg2+ concentration and muscle MgTHs are thus related to whole body Mg2+ homeostasis. Nonetheless, few studies have investigated the regulation of muscle MgTHs under (patho)physiological conditions. Herein, we assessed the relationship between the expression of MgTHs genes (Trpm6, Trpm7, Magt1, Mrs2, Cnnm1-4, Slc41a1-3) and relevant pathways in human sarcopenia, which is one of the most dramatic physiologic changes affecting the human body. Transcriptomic data were compared between young adult (YO, 22 y, n = 11) and old (EL, 73 y, n = 13) men from the PROOF cohort. MgTH mRNA levels did not change with aging, with the exception of a slight decrease for Slc41a3. Nevertheless, interindividual variations of mRNA levels revealed strong correlations between MgTHs in the YO group, while few were maintained in the EL muscle. Moreover, in the YO muscle, different clusters of MgTH mRNAs strongly correlated with divers physiological (BMI, blood pressure) and muscle characteristics (intramyocellular droplets, capillarization); however, most correlations changed or disappeared in the EL muscle. Further investigations of the whole transcriptome identified several sets of mRNAs correlated with defined MgTHs. There again was a sharp difference between YO and EL muscles, as the number of mRNAs correlated with MgTHs strongly decreased with aging. Gene ontology analyses of these sets of correlated mRNAs revealed 6 biological processes common to YO and EL, 3 specific to the YO (RNA processing, translation, respiration), and 2 (regulation of catabolic process, Wnt signaling) to the EL muscle. Overall, these observations lead to questions about potential resilience to muscle Mg2+ homeostasis in the elderly.
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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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The 808 nm and 980 nm infrared laser irradiation affects spore germination and stored calcium homeostasis: A comparative study using delivery hand-pieces with standard (Gaussian) or flat-top profile.
Ferrando, S, Agas, D, Mirata, S, Signore, A, De Angelis, N, Ravera, S, Utyuzh, AS, Parker, S, Sabbieti, MG, Benedicenti, S, et al
Journal of photochemistry and photobiology. B, Biology. 2019;:111627
Abstract
Photobiomodulation relies on the transfer of energy from incident photons to a cell photoacceptor. For many years the concept of photobiomodulation and its outcome has been based upon a belief that the sole receptor within the cell was the mitochondrion. Recently, it has become apparent that there are other photoacceptors operating in different regions of the electromagnetic spectrum. Alternative photoacceptors would appear to be water and mechanisms regulating calcium homeostasis, despite a direct effect of laser photonic energy on intracellular calcium concentration outwith mitochondrial activity or influence, have not been clearly demonstrated. Therefore, to increase the knowledge of intracellular‑calcium and laser photon interaction, as well as to demonstrate differences in irradiation profiles with modern hand-pieces, we tested and compared the photobiomodulatory effect of 808 nm and 980 nm diode laser light by low- and higher-energy (60s, 100 mW/cm2, 100 mW/cm2, 500 mW/cm2, 1000 mW/cm2, 1500 mW/cm2, 2000 mW/cm2) irradiated with a "standard" (Gaussian fluence distribution) hand-piece or with a "flat-top" (uniform fluence) hand-piece. For this purpose, we used the eukaryote unicellular-model Dictyostelium discoideum. The 808 nm and 980 nm infrared laser light, at the energy tested directly affect the stored Ca2+ homeostasis, independent of the mitochondrial respiratory chain activities. From an organism perspective, the effect on Ca2+-dependent signal transduction as the regulator of spore germination in Dictyostelium, demonstrates how a cell can respond quickly to the correct laser photonic stimulus through a different cellular pathway than the known light-chromophore(mitochondria) interaction. Additionally, both hand-piece designs tested were able to photobiomodulate the D. discoideum cell; however, the hand-piece with a flat-top profile, through uniform fluence levels allows more effective and reproducible effects.
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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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Iron Deficiency and Iron Homeostasis in Low Birth Weight Preterm Infants: A Systematic Review.
Moreno-Fernandez, J, Ochoa, JJ, Latunde-Dada, GO, Diaz-Castro, J
Nutrients. 2019;(5)
Abstract
Iron is an essential micronutrient that is involved in many functions in humans, as it plays a critical role in the growth and development of the central nervous system, among others. Premature and low birth weight infants have higher iron requirements due to increased postnatal growth compared to that of term infants and are, therefore, susceptible to a higher risk of developing iron deficiency or iron deficiency anemia. Notwithstanding, excess iron could affect organ development during the postnatal period, particularly in premature infants that have an immature and undeveloped antioxidant system. It is important, therefore, to perform a review and analyze the effects of iron status on the growth of premature infants. This is a transversal descriptive study of retrieved reports in the scientific literature by a systematic technique. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were adapted for the review strategy. The inclusion criteria for the studies were made using the PICO (population, intervention, comparison, outcome) model. Consequently, the systematic reviews that included studies published between 2008-2018 were evaluated based on the impact of iron status on parameters of growth and development in preterm infants.
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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.