Meta‐analysis of literature data on mineral and trace element requirements of fish was performed with the major objectives of identifying appropriate response criteria and the factors affecting the ...minimal dietary inclusion levels. The primary data set included 25 studies on available P, 20 on Ca, 24 on Mg, 5 on K, 37 for Zn, 23 for Se, 19 for Mn, 16 for Fe and 13 for Cu. Broken line regression analysis with linear plateau model (P, Ca, Mg and K) or two‐linear line model (Zn, Cu, Fe, Mn and Se) was used for determining the minimal dietary inclusion levels. Vertebral mineral concentration (P, Ca, Zn and Mn), whole‐body mineral levels (Mg, K and Fe) and hepatic enzyme activity (Se) were found to be the most appropriate criteria for the respective minerals analysed. In general, weight gain as the criterion resulted in a lower estimate (by 18–42%) than those obtained using whole‐body or vertebral mineral concentrations as response criteria. The analysis also showed that different fish species do not show large variations in the mineral and trace element concentrations in the whole body and tissues. Factors such as species group and digestive physiology, type of experimental diet used and dietary interactions, type of mineral source and mineral concentration of water were found to affect the minimal dietary inclusion levels of certain minerals. Besides the meta‐analysis, research needs in mineral nutrition of fish with reference to growing changes in dietary strategies and rearing systems are discussed.
Glioblastoma (GBM) is one of the most aggressive tumors. Numerous studies in the field of immunotherapy have focused their efforts on identifying various pathways linked with tumor-induced ...immunosuppression. Recent research has demonstrated that metabolic reprogramming in a tumor can contribute towards immune tolerance. To begin to understand the interface between metabolic remodeling and the immune-suppressive state in GBM, we performed a focused, integrative analysis coupling metabolomics with gene-expression profiling in patient-derived GBM (
n
= 80) and compared them to low-grade astrocytoma (LGA;
n
= 28). Metabolic intermediates of tryptophan, arginine, prostaglandin, and adenosine emerged as immuno-metabolic nodes in GBM specific to the mesenchymal and classical molecular subtypes of GBM. Integrative analyses emphasized the importance of downstream metabolism of several of these metabolic pathways in GBM. Using CIBERSORT to analyze immune components from the transcriptional profiles of individual tumors, we demonstrated that tryptophan and adenosine metabolism resulted in an accumulation of Tregs and M2 macrophages, respectively, and was recapitulated in mouse models. Furthermore, we extended these findings to preclinical models to determine their potential utility in defining the biologic and/or immunologic consequences of the identified metabolic programs. Collectively, through integrative analysis, we uncovered multifaceted ways by which metabolic reprogramming may contribute towards immune tolerance in GBM, providing the framework for further investigations designed to determine the specific immunologic consequence of these metabolic programs and their therapeutic potential.
Atlantic salmon were fed diets containing graded levels of EPA + DHA (1·0, 1·3, 1·6 and 3·5 % in the diet) and one diet with 1·3 % of EPA + DHA with reduced total fat content. Fish were reared in sea ...cages from about 275 g until harvest size (about 5 kg) and were subjected to delousing procedure (about 2·5 kg), with sampling pre-, 1 h and 24 h post-stress. Delousing stress affected plasma cortisol and hepatic mRNA expression of genes involved in oxidative stress and immune response, but with no dietary effects. Increasing EPA + DHA levels in the diet increased the trace mineral levels in plasma and liver during mechanical delousing stress period and whole body at harvest size. The liver Se, Zn, Fe, Cu, and Mn and plasma Se levels were increased in fish fed a diet high in EPA + DHA (3·5 %) upon delousing stress. Furthermore, increased dietary EPA + DHA caused a significant increase in mRNA expression of hepcidin antimicrobial peptide (HAMP), which is concurrent with downregulated transferrin receptor (TFR) expression levels. High dietary EPA + DHA also significantly increased the whole-body Zn, Se, and Mn levels at harvest size fish. Additionally, the plasma and whole-body Zn status increased, respectively, during stress and at harvest size in fish fed reduced-fat diet with less EPA + DHA. As the dietary upper limits of Zn and Se are legally added to the feeds and play important roles in maintaining fish health, knowledge on how the dietary fatty acid composition and lipid level affect body stores of these minerals is crucial for the aquaculture industry.
In our work to investigate the photophysical, antioxidant, antibacterial, DFT and topological analysis of four C-alkyl calix4resorcinarenes (3a-3d - C4RAs). The photophysical properties of C4RAs in ...selected solvents were recorded using both UV-Visible and fluorescence spectral studies. The absorption and emission maximum of four C4RAs were observed around 280 nm and 318 nm in selected solvents. The solvatochromism with selected solvents were analysed from the plot between Stoke’s shift and E
T
N
. The antioxidant activity and antibacterial activity of four C4RAs were evaluated by phosphomolybdate assay and Kirby-Bauer method. The structure of four C4RAs was optimized using DFT B3LYP 6-311G method to calculating the various theoretical parameters in the gas phase. The stability, reactivity, formation of hydrogen bond, donor-acceptor interactions were reported from the interpretation of theoretical values. The non-covalent interactions of four C4RAs were characterized by LOL and ELF topological analysis.
Graphical Abstract
Responses in micro-mineral metabolism to changes in dietary ingredient composition and inclusion of a micro-mineral premix (Fe, Cu, Mn, Zn and Se) were studied in rainbow trout. In a 2 x 2 factorial ...design, triplicate groups of rainbow trout (initial weight: 20 g) were fed over 12 weeks at 17°C a fishmeal-based diet (M) or a plant-ingredient based diet (V), with or without inclusion of a mineral premix. Trout fed the V vs. M diet had lower feed intake, growth, hepato-somatic index, apparent availability coefficient (AAC) of Fe, Cu, Mn and Zn and also lower whole body Se and Zn concentration, whereas whole body Fe and Cu and plasma Fe concentrations were higher. Feeding the V diet increased intestinal ferric reductase activity; at transcriptional level, hepatic hepcidin expression was down-regulated and ferroportin 1 was up-regulated. Transcription of intestinal Cu-transporting ATPases and hepatic copper transporter1 were higher in V0 compared to other groups. Among the hepatic metalo-enzyme activities assayed, only Se-dependent glutathione peroxidase was affected, being lower in V fed fish. Premix inclusion reduced the AAC of Fe, Cu and Zn; increased the whole body concentration of all micro- minerals; up-regulated hepatic hepcidin and down-regulated intestinal ferroportin 1 transcription; and reduced the transcription of Cu-transporting ATPases in the intestine. Overall, the regulation of micro-mineral metabolism in rainbow trout, especially Fe and Cu, was affected both by a change in ingredient composition and micro-mineral premix inclusion.
There has been considerable scientific effort dedicated to understanding the biologic consequence and therapeutic implications of aberrant tryptophan metabolism in brain tumors and neurodegenerative ...diseases. A majority of this work has focused on the upstream metabolism of tryptophan; however, this has resulted in limited clinical application. Using global metabolomic profiling of patient-derived brain tumors, we identify the downstream metabolism of tryptophan and accumulation of quinolinate (QA) as a metabolic node in glioblastoma and demonstrate its critical role in promoting immune tolerance. QA acts as a metabolic checkpoint in glioblastoma by inducing NMDA receptor activation and Foxo1/PPARγ signaling in macrophages, resulting in a tumor supportive phenotype. Using a genetically-engineered mouse model designed to inhibit production of QA, we identify kynureninase as a promising therapeutic target to revert the potent immune suppressive microenvironment in glioblastoma. These findings offer an opportunity to revisit the biologic consequence of this pathway as it relates to oncogenesis and neurodegenerative disease and a framework for developing immune modulatory agents to further clinical gains in these otherwise incurable diseases.
Despite advances in molecularly characterizing glioblastoma (GBM), metabolic alterations driving its aggressive phenotype are only beginning to be recognized. Integrative cross-platform analysis ...coupling global metabolomic and gene expression profiling on patient-derived glioma identified fatty acid β-oxidation (FAO) as a metabolic node in GBM. We determined that the biologic consequence of enhanced FAO is directly dependent upon tumor microenvironment. FAO serves as a metabolic cue to drive proliferation in a β-HB/GPR109A dependent autocrine manner in nutrient favorable conditions, while providing an efficient, alternate source of ATP only in nutrient unfavorable conditions. Rational combinatorial strategies designed to target these dynamic roles FAO plays in gliomagenesis resulted in necroptosis-mediated metabolic synthetic lethality in GBM. In summary, we identified FAO as a dominant metabolic node in GBM that provides metabolic plasticity, allowing these cells to adapt to their dynamic microenvironment. Combinatorial strategies designed to target these diverse roles FAO plays in gliomagenesis offers therapeutic potential in GBM.
Abstract
Background
Although considerable progress has been made in understanding molecular alterations driving gliomagenesis, the diverse metabolic programs contributing to the aggressive phenotype ...of glioblastoma remain unclear. The aim of this study was to define and provide molecular context to metabolic reprogramming driving gliomagenesis.
Methods
Integrative cross-platform analyses coupling global metabolomic profiling with genomics in patient-derived glioma (low-grade astrocytoma LGA; n = 28 and glioblastoma n = 80) were performed. Identified programs were then metabolomically, genomically, and functionally evaluated in preclinical models.
Results
Clear metabolic programs were identified differentiating LGA from glioblastoma, with aberrant lipid, peptide, and amino acid metabolism representing dominant metabolic nodes associated with malignant transformation. Although the metabolomic profiles of glioblastoma and LGA appeared mutually exclusive, considerable metabolic heterogeneity was observed in glioblastoma. Surprisingly, integrative analyses demonstrated that O6-methylguanine-DNA methyltransferase methylation and isocitrate dehydrogenase mutation status were equally distributed among glioblastoma metabolic profiles. Transcriptional subtypes, on the other hand, tightly clustered by their metabolomic signature, with proneural and mesenchymal tumor profiles being mutually exclusive. Integrating these metabolic phenotypes with gene expression analyses uncovered tightly orchestrated and highly redundant transcriptional programs designed to support the observed metabolic programs by actively importing these biochemical substrates from the microenvironment, contributing to a state of enhanced metabolic heterotrophy. These findings were metabolomically, genomically, and functionally recapitulated in preclinical models.
Conclusion
Despite disparate molecular pathways driving the progression of glioblastoma, metabolic programs designed to maintain its aggressive phenotype remain conserved. This contributes to a state of enhanced metabolic heterotrophy supporting survival in diverse microenvironments implicit in this malignancy.
Mineral nutrition and bone health in salmonids Baeverfjord, Grete; Antony Jesu Prabhu, P.; Fjelldal, Per Gunnar ...
Reviews in aquaculture,
August 2019, Letnik:
11, Številka:
3
Journal Article
Recenzirano
Odprti dostop
In the recent years, challenges faced in salmonid farming with regard to deformities have helped to improve our knowledge on skeletal biology and development of bone health in salmonids. Different ...nutritional, genetic and environmental factors are associated with skeletal deformities in salmonids and other fish species. Minerals are a group of essential nutrients having a vital role to play in skeletal development, growth and remodelling. The knowledge generated thus far on the structural and functional importance of minerals in salmonid bone health is largely restricted to phosphorus. A brief account of dietary phosphorus‐related bone deformities encountered in salmonids, critical life stages for the development of bone deformities, recent developments in the understanding of their aetiology and dietary phosphorus levels required to improve bone health are presented. The effect of increased dietary level of phosphorus in reducing bone health disorders under conditions of improved feed conversion efficiency and use of triploids in salmon farming are illustrated with help of metadata analysis from literature. With regard to the role of other essential minerals (macro‐ and micro‐) impacting bone health in salmonids, data available are extremely limited and hence information on other fish species and mammals is summarized in relation to bone development and incidence of deformities. The need to improve mineral bioavailability, utilization and reduce effluent mineral load is presented in brief with example from Norwegian salmon farming. Refinements in mineral requirement recommendations for salmonids and advanced methodologies for studying aetiology of skeletal anomalies, bone mineral status, skeletal development and deformities are also discussed.
We studied the effects of supplementing a plant-ingredient based rainbow trout broodstock diet with different forms of selenium (Se) on reproductive performance, parental Se transfer and antioxidant ...metabolism in their progeny before first-feeding. Three groups of rainbow trout were fed a diet either without selenium supplementation (NC, basal Se level: 0.3 ppm) or supplemented with 0.3 ppm Se either in the form of sodium selenite (SS) or as hydroxy-selenomethionine (SO, dietary Se level: 0.7 ppm) over a 6-month period prior to spawning. In Se-supplemented groups, the total number of females spawning was significantly higher compared to the negative control group and the females fed SO began to spawn earlier compared to females fed SS or NC. Total Se concentrations were significantly higher in female muscle of SO group. Higher Se concentrations in the oocytes of both Se-supplemented groups confirmed a maternal transfer of Se, while total Se concentrations in milt samples were not significantly different between dietary groups. There was no effect on glutathione peroxidase (GPX) or other antioxidant enzyme activity in the liver of female or male broodstock, whereas in the swim-up fry, GPX activity was significantly higher in both Se-supplemented treatments with the highest activity in the SO group. Se-supplementation enhanced the expression of hepatic SelPa in broodstock males and females along with MsrB1, GPx1a, GPx4a2, CAT, Gclc, Keap1 and MsrB2 in male liver. In swim-up fry, only organic Se-supplementation led to a higher gene expression for SelPa, GPX1a, GPX1b2, CAT and MsrB2. An improvement of the oxidative status in whole-body of swim-up fry could not be confirmed in this study as the GSH/GSSG was even lower in swim-up fry of Se-supplemented groups, whereas the 8-isoprostane levels were lower in the SS group and no effect on protein carbonyl levels could be detected. Organic Se-supplementation led to a significant increase in the α-tocopherol and vitamin C levels in the progeny. These results show that dietary Se in broodstock nutrition influences spawning occurrence and along with the parental transfer, several traits in the progeny are affected.
•Dietary Se affected the number and timing of spawning in rainbow trout females.•Better bioavailability of Se in broodstock diets increased its transfer to the progeny.•Highest GPX activity and mRNA expression of selenoproteins in offspring of broodstock fed organic Se.•Organic Se supplementation increased vitamin E and C levels in progeny.
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