Cardiovascular Metabolomics McGarrah, Robert W; Crown, Scott B; Zhang, Guo-Fang ...
Circulation research,
2018-April-27, Letnik:
122, Številka:
9
Journal Article
Recenzirano
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Disturbances in cardiac metabolism underlie most cardiovascular diseases. Metabolomics, one of the newer omics technologies, has emerged as a powerful tool for defining changes in both global and ...cardiac-specific metabolism that occur across a spectrum of cardiovascular disease states. Findings from metabolomics studies have contributed to better understanding of the metabolic changes that occur in heart failure and ischemic heart disease and have identified new cardiovascular disease biomarkers. As technologies advance, the metabolomics field continues to evolve rapidly. In this review, we will discuss the current state of metabolomics technologies, including consideration of various metabolomics platforms and elements of study design; the emerging utility of stable isotopes for metabolic flux studies; and the use of metabolomics to better understand specific cardiovascular diseases, with an emphasis on recent advances in the field.
Skeletal stem cells (SSCs) are postulated to provide a continuous supply of osteoblasts throughout life. However, under certain conditions, the SSC population can become incorrectly specified or is ...not maintained, resulting in reduced osteoblast formation, decreased bone mass, and in severe cases, osteoporosis. Glutamine metabolism has emerged as a critical regulator of many cellular processes in diverse pathologies. The enzyme glutaminase (GLS) deaminates glutamine to form glutamate—the rate-limiting first step in glutamine metabolism. Using genetic and metabolic approaches, we demonstrate GLS and glutamine metabolism are required in SSCs to regulate osteoblast and adipocyte specification and bone formation. Mechanistically, transaminase-dependent α-ketoglutarate production is critical for the proliferation, specification, and differentiation of SSCs. Collectively, these data suggest stimulating GLS activity may provide a therapeutic approach to expand SSCs in aged individuals and enhance osteoblast differentiation and activity to increase bone mass.
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•Skeletal stem cells increase glutamine metabolism during osteoblast differentiation•Glutamine metabolism regulates osteoblast and adipocyte specification•Mice unable to metabolize glutamine have less bone and increased marrow fat•Amino acid transaminase-derived α-ketoglutarate is critical for SSC proliferation
Skeletal stem cells (SSCs) provide a reservoir of bone-forming osteoblasts throughout life. Yu et al. investigate glutamine metabolism in SSCs. Glutamine-derived α-ketoglutarate supports amino acid biosynthesis and proliferation in SSCs. Inhibiting glutamine metabolism in SSCs results in low bone mass and increased marrow adiposity in mice.
High electrocatalytic activity with tunable luminescence is crucial for the development of electrochemiluminescence (ECL) luminophores. In this study, a porphyrin‐based heterobimetallic 2D metal ...organic framework (MOF), (ZnTCPP)Co2(MeIm) (1), is successfully self‐assembled from the zinc(II) tetrakis(4‐carboxyphenyl)porphine (ZnTCPP) linker and cobalt(II) ions in the presence of 2‐methylimidazole (MeIm) by a facile one‐pot reaction in methanol at room temperature. On the basis of the experimental results and the theoretical calculations, the MOF 1 contains paddle–wheel Co2(‐CO2)4 secondary building units (SBUs) axially coordinated by a MeIm ligand, which is very beneficial to the electron transfer between the Co(II) ions and oxygen. Combining the photosensitizers ZnTCPP and the electroactive Co2(‐CO2)4 SBUs, the 2D MOF 1 possesses an excellent ECL performance, and can be used as a novel ECL probe for rapid nonamplified detection of the RdRp gene of SARS‐CoV‐2 with an extremely low limit of detection (≈30 aM).
A novel porphyrin‐based heterobimetallic 2D MOF, (ZnTCPP)Co2(MeIm) (1) is constructed to act as an excellent electrochemiluminescence probe for rapid nonamplified detection of SARS‐CoV‐2.
A simple and rapid photoelectrochemical (PEC) sensor was developed for the label-free detection of a phosphoprotein (α-casein) based on a zirconium based porphyrinic metal–organic framework (MOF), ...PCN-222, which exhibited an enhanced photocurrent response toward dopamine under the O2-saturated aqueous media. In this work, in terms of PEC measurements and cyclic voltammetry, the PEC behaviors of PCN-222 in aqueous media were thoroughly investigated for the first time. Additionally, in the virtue of the steric hindrance effect from the coordination of the phosphate groups and inorganic Zr–O clusters as binding sites in PCN-222, this biosensor showed high sensitivity for detecting α-casein and the limit of detection (LOD) was estimated to be 0.13 μg mL–1. Moreover, the proposed method provides a promising platform for clinic diagnostic and therapeutics.
Cancer metastasis accounts for the majority of cancer-related deaths and remains a clinical challenge. Metastatic cancer cells generally resemble cells of the primary cancer, but they may be ...influenced by the milieu of the organs they colonize. Here, we show that colorectal cancer cells undergo metabolic reprogramming after they metastasize and colonize the liver, a key metabolic organ. In particular, via GATA6, metastatic cells in the liver upregulate the enzyme aldolase B (ALDOB), which enhances fructose metabolism and provides fuel for major pathways of central carbon metabolism during tumor cell proliferation. Targeting ALDOB or reducing dietary fructose significantly reduces liver metastatic growth but has little effect on the primary tumor. Our findings suggest that metastatic cells can take advantage of reprogrammed metabolism in their new microenvironment, especially in a metabolically active organ such as the liver. Manipulation of involved pathways may affect the course of metastatic growth.
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•Colon cancer liver metastasis upregulates ALDOB, an enzyme for fructose metabolism•Metabolized fructose provides fuel for the central carbon metabolism•Targeting ALDOB or its upstream regulator GATA6 reduces liver metastasis growth•Reducing dietary fructose diminishes liver metastatic growth
Bu et al. show that, during colonization of the liver, the liver environment can cause colon cancer cells (CRC) to undergo metabolic reprogramming by upregulating aldolase B, which enhances fructose metabolism and promotes growth of CRC liver metastases. Targeting aldolase B or reducing dietary fructose reduces liver metastasis growth.
Osteoblast differentiation is sequentially characterized by high rates of proliferation followed by increased protein and matrix synthesis, processes that require substantial amino acid acquisition ...and production. How osteoblasts obtain or maintain intracellular amino acid production is poorly understood. Here, we identify SLC1A5 as a critical amino acid transporter during bone development. Using a genetic and metabolomic approach, we show SLC1A5 acts cell autonomously to regulate protein synthesis and osteoblast differentiation. SLC1A5 provides both glutamine and asparagine which are essential for osteoblast differentiation. Mechanistically, glutamine and to a lesser extent asparagine support amino acid biosynthesis. Thus, osteoblasts depend on
to provide glutamine and asparagine, which are subsequently used to produce non-essential amino acids and support osteoblast differentiation and bone development.
Aims and objectives
To investigate burnout among nurses from Australia and China and explore the effects of resilience and turnover intention on nurse burnout between the two countries.
Background
...Nursing shortages and burnout have become serious problems worldwide in recent years. In both developed and developing countries, such as Australia and China, nurse burnout levels are high and therefore attract concern from nurse managers, hospital administrators, nurse educators and researchers. However, few studies have been conducted exploring the differences in burnout and its predictors between Australian and Chinese nurses, particularly investigating the differences in the effect sizes of the predictors.
Design
A comparative cross‐sectional design was employed.
Methods
A total of 100 Australian nurses and 197 Chinese nurses participated in the study. Australian participants completed an online questionnaire, while Chinese participants completed a hardcopy questionnaire. Burnout, resilience and turnover intention were measured.
Results
Burnout was worse for Australian participants than Chinese participants. Only having turnover intention significantly predicted burnout in Australian participants, while low resilience, having turnover intention and low level of regular exercise strongly predicted burnout in Chinese participants. The effect size of turnover intention on burnout in the Australian group was almost twice that of the Chinese group.
Conclusion
The findings of this study show that there are differences in burnout between Australian and Chinese nurses. The effects of resilience and turnover intention on burnout between the two groups are also identified.
Relevance to clinical practice
The differences in nurse burnout and the effects of resilience and turnover intention on burnout should be better understood by nurse managers from Australia and China. Moreover, developing effective strategies relevant to their own country to reduce nurse burnout is recommended.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent tumorigenic growth, but the role of KRAS in supporting autophagy has not been established. We show that, to ...our surprise, suppression of KRAS increased autophagic flux, as did pharmacological inhibition of its effector ERK MAPK. Furthermore, we demonstrate that either KRAS suppression or ERK inhibition decreased both glycolytic and mitochondrial functions. We speculated that ERK inhibition might thus enhance PDAC dependence on autophagy, in part by impairing other KRAS- or ERK-driven metabolic processes. Accordingly, we found that the autophagy inhibitor chloroquine and genetic or pharmacologic inhibition of specific autophagy regulators synergistically enhanced the ability of ERK inhibitors to mediate antitumor activity in KRAS-driven PDAC. We conclude that combinations of pharmacologic inhibitors that concurrently block both ERK MAPK and autophagic processes that are upregulated in response to ERK inhibition may be effective treatments for PDAC.
The plant microbiota play a key role in plant productivity, nutrient uptake, resistance to stress and flowering. The flowering of moso bamboo has been a focus of study. The mechanism of flowering is ...related to nutrient uptake, temperature, hormone balance and regulation of key genes. However, the connection between microbiota of moso bamboo and its flowering is unknown. In this study, samples of rhizosphere soil, rhizomes, roots and leaves of flowering and nonflowering plants were collected, and 16S rRNA amplicon Illumina sequencing was utilized to separate the bacterial communities associated with different flowering stages of moso bamboo. We identified 5442 OTUs, and the number of rhizosphere soil OTUs was much higher than those of other samples. Principal component analysis (PCA) and hierarchical clustering (Bray Curtis dis) analysis revealed that the bacterial microorganisms related to rhizosphere soil and endophytic tissues of moso bamboo differed significantly from those in bulk soil and rhizobacterial and endosphere microbiomes. In addition, the PCA analyses of root and rhizosphere soil revealed different structures of microbial communities between bamboo that is flowering and not flowering. Through the analysis of core microorganisms, it was found that Flavobacterium, Bacillus and Stenotrophomonas played an important role in the absorption of N elements, which may affect the flowering time of moso bamboo. Our results delineate the complex host-microbe interactions of this plant. We also discuss the potential influence of bacterial microbiome in flowering, which can provide a basis for the development and utilization of moso bamboo.
Chlorpyrifos is a pesticide frequently detected in food and has been reported to disturb endocrine and gut health, which was regulated by gut microbiota and enteroendocrine cells. In this study, ...newly weaned (3 week) and adult (8 week) male rats fed a normal- or high- fat diet were chronically exposed to 0.3 mg chlorpyrifos/kg bodyweight/day. The effects of chlorpyrifos exposure on serum hormone levels, proinflammatory cytokines and gut microbiota were evaluated. Chronic exposure to chlorpyrifos significantly decreased the concentrations of luteinizing hormone, follicule stimulating hormone and testosterone, which was found only in the normal-fat diet. The counteracted effect of high-fat diet was also found in gut hormones and proinflammatory cytokines. Significantly higher concentrations of glucagon-like peptide-1, pancreatic polypeptide, peptide tyrosine tyrosine (PYY), ghrelin, gastric inhibitory poly-peptide, IL-6, monocyte chemoattractant protein-1, and TNF-α were found in rats exposed to chlorpyrifos beginning at newly weaned, whereas only the PYY, ghrelin and IL-6 concentrations increased significantly in rats exposed in adulthood. Furthermore, a decrease in epinephrine induced by chlorpyrifos exposure was found in rats exposed to chlorpyrifos beginning at newly weaned, regardless of their diet. Chlorpyrifos-induced disturbances in the microbiome community structure were more apparent in rats fed a high-fat diet and exposed beginning at newly weaned. The affected bacteria included short-chain fatty acid-producing bacteria (Romboutsia, Turicibacter, Clostridium sensu stricto 1, norank_f_Coriobacteriaceae, Faecalibaculum, Parasutterella and norank_f__Erysipelotrichaceae), testosterone-related genus (Turicibacter, Brevibacterium), pathogenic bacteria (Streptococcus), and inflammation-related bacteria (unclassified_f__Ruminococcaceae, Ruminococcaceae_UCG-009, Parasutterella, Oscillibacter), which regulated the endocrine system via the hypothalamic-pituitary-adrenal axis, as well as the immune response and gut barrier. Early exposure accelerated the endocrine-disturbing effect and immune responses of chlorpyrifos, although these effects can be eased or recovered by a high-fat diet. This study helped clarify the relationship between disrupted endocrine function and gut microbiota dysbiosis induced by food contaminants such as pesticides.
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•Early exposure exhibits a much stronger endocrine-disturbing effect of chlorpyrifos.•Effects of chlorpyrifos on hormones and immune can be relieved by a high-fat diet.•Chlorpyrifos regulate the HPT axis and CNS by affecting the gut microbiota.•Chlorpyrifos affect the secretion of gut hormones especially exposure from young.
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