The failing human heart is characterized by metabolic abnormalities, but these defects remains incompletely understood. In animal models of heart failure there is a switch from a predominance of ...fatty acid utilization to the more oxygen-sparing carbohydrate metabolism. Recent studies have reported decreases in myocardial lipid content, but the inclusion of diabetic and nondiabetic patients obscures the distinction of adaptations to metabolic derangements from adaptations to heart failure per se.
We performed both unbiased and targeted myocardial lipid surveys using liquid chromatography-mass spectroscopy in nondiabetic, lean, predominantly nonischemic, advanced heart failure patients at the time of heart transplantation or left ventricular assist device implantation. We identified significantly decreased concentrations of the majority of myocardial lipid intermediates, including long-chain acylcarnitines, the primary subset of energetic lipid substrate for mitochondrial fatty acid oxidation. We report for the first time significantly reduced levels of intermediate and anaplerotic acyl-coenzyme A (CoA) species incorporated into the Krebs cycle, whereas the myocardial concentration of acetyl-CoA was significantly increased in end-stage heart failure. In contrast, we observed an increased abundance of ketogenic β-hydroxybutyryl-CoA, in association with increased myocardial utilization of β-hydroxybutyrate. We observed a significant increase in the expression of the gene encoding succinyl-CoA:3-oxoacid-CoA transferase, the rate-limiting enzyme for myocardial oxidation of β-hydroxybutyrate and acetoacetate.
These findings indicate increased ketone utilization in the severely failing human heart independent of diabetes mellitus, and they support the role of ketone bodies as an alternative fuel and myocardial ketone oxidation as a key metabolic adaptation in the failing human heart.
Macrophages specialize in removing lipids and debris present in the atherosclerotic plaque. However, plaque progression renders macrophages unable to degrade exogenous atherogenic material and ...endogenous cargo including dysfunctional proteins and organelles. Here we show that a decline in the autophagy-lysosome system contributes to this as evidenced by a derangement in key autophagy markers in both mouse and human atherosclerotic plaques. By augmenting macrophage TFEB, the master transcriptional regulator of autophagy-lysosomal biogenesis, we can reverse the autophagy dysfunction of plaques, enhance aggrephagy of p62-enriched protein aggregates and blunt macrophage apoptosis and pro-inflammatory IL-1β levels, leading to reduced atherosclerosis. In order to harness this degradative response therapeutically, we also describe a natural sugar called trehalose as an inducer of macrophage autophagy-lysosomal biogenesis and show trehalose's ability to recapitulate the atheroprotective properties of macrophage TFEB overexpression. Our data support this practical method of enhancing the degradative capacity of macrophages as a therapy for atherosclerotic vascular disease.
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-PEGylated-thiazolium salt is used as efficient catalyst for the benzoin condensation. The catalyst was synthesized by reaction of activated polyethylene glycol 10,000 (PEG-10000) with ...4-methyl-5-thiazoleethanol (sulfurol). Reaction mixture undergoes temperature-assisted phase transition and catalyst separated by simple filtration. After reaction course, catalyst can be recycled and reused without any apparent loss of activity which makes this process cost effective and hence ecofriendly. Synthesized benzoins and acyloins by this method have been characterized on the basis of melting point and
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H-NMR spectral studies.
Graphic Abstract
Understanding and modelling the wettability of tight rocks is essential for designing fracturing and treatment fluids. In this paper, we measure and analyze spontaneous imbibition of water and oil ...into five twin core plugs drilled from the cores of a well drilled in the Montney Formation, an unconventional oil and gas play in the Western Canadian Sedimentary Basin. We characterize the samples by measuring the mineralogy using XRD（x-ray diffraction）, total organic carbon content, porosity, and permeability. Interestingly, the equilibrated water uptake of the five samples is similar, while, their oil uptake increases by increasing the core porosity and permeability. We define two wettability indices for the oil phase based on the slope and equilibrium values of water and oil imbibition curves. Both indices increase by increasing porosity and permeability, with the slope affinity index showing a stronger correlation. This observation suggests that part of the pore network has a stronger affinity to oil than to water. We also observe that the two indices decrease by increasing neutron porosity and gamma ray parameters measured by wireline logging tools. The samples with higher gamma ray and neutron porosity are expected to have greater clay content, and thus less effective porosity and permeability.
Micromodel flooding is a cost-effective method to investigate enhanced oil recovery. In this study, we apply Lauryl Betaine as an amphoteric surfactant to the injected fluids into the micromodel and ...compare the results with conventional EOR techniques such as water flooding, solvent flooding, and microemulsion flooding. First, we determined the optimal flow rate of injected fluid into the micromodel to represent fluid flow in the formation. Next, we did water flooding with varying salinities. Next, we did solvent flooding with two different ratios of solvents. Condensate and hexane are the solvents we applied. Next, we did surfactant flooding using Lauryl Betaine. Surfactant flooding tests are conducted using different salinity and surfactant concentration (Cs). Finally, we did microemulsion flooding. The results show that surfactant flooding at high salinity using Lauryl Betaine leads to highest oil recovery among all tested EOR methods. Besides, the results indicate that addition of Lauryl Betaine to the injected brine leads to higher breakthrough time (BT).
Yeast histone H2A is phosphorylated on Ser129 upon DNA damage, an event required for efficient repair. We show that phosphorylation occurs rapidly over a large region around DNA double-strand breaks ...(DSBs). Histone H4 acetylation is also important for DSB repair, and we found that the NuA4 HAT complex associates specifically with phospho-H2A peptides. A single NuA4 subunit, Arp4, is responsible for the interaction. The NuA4 complex is recruited to a DSB concomitantly with the appearance of H2A P-Ser129 and Arp4 is important for this binding. Arp4 is also a subunit of the Ino80 and Swr1 chromatin remodeling complexes, which also interact with H2A P-Ser129 and are recruited to DSBs. This association again requires Arp4 but also prior NuA4 recruitment and action. Thus, phosphorylation of H2A at DNA damage sites creates a mark recognized by different chromatin modifiers. This interaction leads to stepwise chromatin reconfiguration, allowing efficient DNA repair.
At the end of each diet period, dynamic cardiac positron emission tomography-computed tomography (PET/CT) imaging in conjunction with 11Cpalmitate, ИС acetate, and 15OH2O was performed to ...noninvasively evaluate myocardial fatty acid metabolism, oxygen consumption, external efficiency (stroke work in relationship to oxygen consumption), and flow reserve (increase in myocardial perfusion after adenosine administration). ...during the ketogenic diet period, participants in the study by Luong 2 lost about 2 kg of body weight during just 3 weeks. ...ketones reduce glucose oxidation 10 and are an even more efficient substrate than fatty acids and ketones.
Although research on high-density lipoprotein (HDL) has historically focused on atherosclerotic coronary disease, there exists untapped potential of HDL biology for the treatment of heart failure. ...Anti-oxidant, anti-inflammatory, and endothelial protective properties of HDL could impact heart failure pathogenesis. HDL-associated proteins such as apolipoprotein A-I and M may have significant therapeutic effects on the myocardium, in part by modulating signal transduction pathways and sphingosine-1-phosphate biology. Furthermore, because heart failure is a complex syndrome characterized by multiple comorbidities, there are complex interactions between heart failure, its comorbidities, and lipoprotein homeostatic mechanisms. In this review, we will discuss the effects of heart failure and associated comorbidities on HDL, explore potential cardioprotective properties of HDL, and review novel HDL therapeutic targets in heart failure.
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