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Currently, the use of nanotechnology opens up new opportunities to influence the processes of anaerobic glycolysis and the activity of hexose monophosphate reactions in preserved erythrocytes. Components containing donor red blood cells on CPDA-1 preservative were examined. Modified solutions of 0.9% NaCl and with 5% glucose were used as resuspending solutions. The solutions were treated with magnetite nanoparticles (ICNB brand) by the Belousov method. The amounts of 2,3-DPG, ATP, reduced glutathione, and glutathione peroxidase were determined by spectrophotometry. This study opens up new possibilities for increasing the shelf life and functional activity of preserved erythrocytes. The study showed a reliable increase in ATP and reduced glutathione, a decrease in 2,3-DPG and glutathione peroxidase. It was found that the activation of anaerobic glycolysis was less pronounced in tests with modified physiological saline than in tests with glucose solution. On the contrary, the pentose glucose oxidation cycle prevailed. A comprehensive analysis of the data obtained indicates the membrane-protective effect of the modified resuspending solutions. The membrane-protective effect is due to an increase in ATP and reduced glutathione, which ensures the redox potential of the cell in an equilibrium state. Magnetite nanoparticles (ICNB) change the mobility and orientation of hydrogen protons in resuspending solutions. Thispolarizes the aqueous sector of the erythrocyte microenvironment due to van der Waals forces, which is the main reason for activation of ATP phosphate residue hydrolysis and switching of intracellular enzymes regulating anaerobic glycolysis and pentose phosphate cycle into the active state. As a result, transmembrane metabolism and metabolism change, the energy state of erythrocytes changes, and enzymes are activated. All this has a significant impact on the energy supply of preserved red blood cells and preservation of their functional activity under storage conditions at 2 to 6 ºС. [ABSTRACT FROM AUTHOR]

Abstract HIV‐1 infects lymphoid and myeloid cells, which can harbor a latent proviral reservoir responsible for maintaining lifelong infection. Glycolytic metabolism has been identified as a determinant of susceptibility to HIV‐1 infection, but its role in the development and maintenance of HIV‐1 latency has not been elucidated. By combining transcriptomic, proteomic, and metabolomic analyses, we here show that transition to latent HIV‐1 infection downregulates glycolysis, while viral reactivation by conventional stimuli reverts this effect. Decreased glycolytic output in latently infected cells is associated with downregulation of NAD+/NADH. Consequently, infected cells rely on the parallel pentose phosphate pathway and its main product, NADPH, fueling antioxidant pathways maintaining HIV‐1 latency. Of note, blocking NADPH downstream effectors, thioredoxin and glutathione, favors HIV‐1 reactivation from latency in lymphoid and myeloid cellular models. This provides a “shock and kill effect” decreasing proviral DNA in cells from people living with HIV/AIDS. Overall, our data show that downmodulation of glycolysis is a metabolic signature of HIV‐1 latency that can be exploited to target latently infected cells with eradication strategies.

HIV‐1 infects lymphoid and myeloid cells, which can harbor a latent proviral reservoir responsible for maintaining lifelong infection. Glycolytic metabolism has been identified as a determinant of susceptibility to HIV‐1 infection, but its role in the development and maintenance of HIV‐1 latency has not been elucidated. By combining transcriptomic, proteomic, and metabolomic analyses, we here show that transition to latent HIV‐1 infection downregulates glycolysis, while viral reactivation by conventional stimuli reverts this effect. Decreased glycolytic output in latently infected cells is associated with downregulation of NAD+/NADH. Consequently, infected cells rely on the parallel pentose phosphate pathway and its main product, NADPH, fueling antioxidant pathways maintaining HIV‐1 latency. Of note, blocking NADPH downstream effectors, thioredoxin and glutathione, favors HIV‐1 reactivation from latency in lymphoid and myeloid cellular models. This provides a "shock and kill effect" decreasing proviral DNA in cells from people living with HIV/AIDS. Overall, our data show that downmodulation of glycolysis is a metabolic signature of HIV‐1 latency that can be exploited to target latently infected cells with eradication strategies. SYNOPSIS: The upregulation of glycolysis in activated cells favors HIV‐1 infection and initial viral replication. This study discovers that, to transit into a latent form, which can shield the virus from immunity and antiretroviral drugs, HIV‐1 needs to downregulate glycolysis. Restoration of glycolytic activity is required for HIV‐1 reactivation from latency.Latently infected cells rely on pentose phosphate metabolism and its downstream effectors, i.e., the antioxidant glutathione and thioredoxin pathways, for their survival.Preferential targeting of latently infected cells with drugs inhibiting thioredoxin and glutathione pathways leads to both HIV‐1 reactivation from latency and death of infected cells. [ABSTRACT FROM AUTHOR]

Inhibitors of glycogen breakdown regulate glucose homeostasis by limiting glucose production in diabetes. Here we demonstrate that restrained glycogen breakdown also inhibits cancer cell proliferation and induces apoptosis through limiting glucose oxidation, as well as nucleic acid and de novo fatty acid synthesis. Increasing doses (50-100 microM) of the glycogen phosphorylase inhibitor CP-320626 inhibited [1,2-(13)C(2)]glucose stable isotope substrate re-distribution among glycolysis, pentose and de novo fatty acid synthesis in MIA pancreatic adenocarcinoma cells. Limited oxidative pentose-phosphate synthesis, glucose contribution to acetyl CoA and de novo fatty acid synthesis closely correlated with decreased cell proliferation. The stable isotope-based dynamic metabolic profile of MIA cells indicated a significant dose-dependent decrease in macromolecule synthesis, which was detected at lower drug doses and before the appearance of apoptosis markers. Normal fibroblasts (CRL-1501) did not show morphological or metabolic signs of apoptosis likely due to their slow rate of growth and metabolic activity. This indicates that limiting carbon re-cycling and rapid substrate mobilisation from glycogen may be an effective and selective target site for new drug development in rapidly dividing cancer cells. In conclusion, pancreatic cancer cell growth arrest and death are closely associated with a characteristic decrease in glycogen breakdown and glucose carbon re-distribution towards RNA/DNA and fatty acids during CP-320626 treatment.

Bacteroidaceae are common gut microbiota members in all warm-blooded animals. However, if Bacteroidaceae are to be used as probiotics, the species selected for different hosts should reflect the natural distribution. In this study, we therefore evaluated host adaptation of bacterial species belonging to the family Bacteroidaceae. B. dorei, B. uniformis, B. xylanisolvens, B. ovatus, B. clarus, B. thetaiotaomicron and B. vulgatus represented human-adapted species while B. gallinaceum, B. caecigallinarum, B. mediterraneensis, B. caecicola, M. massiliensis, B. plebeius and B. coprocola were commonly detected in chicken but not human gut microbiota. There were 29 genes which were present in all human-adapted Bacteroides but absent from the genomes of all chicken isolates, and these included genes required for the pentose cycle and glutamate or histidine metabolism. These genes were expressed during an in vitro competitive assay, in which human-adapted Bacteroides species overgrew the chicken-adapted isolates. Not a single gene specific for the chicken-adapted species was found. Instead, chicken-adapted species exhibited signs of frequent horizontal gene transfer, of KUP, linA and sugE genes in particular. The differences in host adaptation should be considered when the new generation of probiotics for humans or chickens is designed.

Glucagon-like peptide-1 (GLP-1, 7-36) is capable of restoring normal glucose tolerance in aging, glucose-intolerant Wistar rats and is a potent causal factor in differentiation of human islet duodenal homeobox-1-expressing cells into insulin-releasing β cells. Here we report stable isotope-based dynamic metabolic profiles of rat pancreatic epithelial (ARIP) and human ductal tumor (PANC-1) cells responding to 10 nM GLP-1 treatment in 48 h cultures. Macromolecule synthesis patterns and substrate flow measurements using gas chromatography/mass spectrometry (MS) and the stable [1,2-13C2]glucose isotope as the tracer showed that GLP-1 induced a significant 20% and 60% increase in de novo fatty acid palmitate synthesis in ARIP and PANC-1 cells, respectively, and it also induced a significant increase in palmitate chain elongation into stearate utilizing glucose as the primary substrate. Distribution of 13C in other metabolites indicated no changes in the rates of nucleic acid ribose synthesis, glutamate oxidation, or lactate production. Tandem high-performance liquid chromatography-ion trap MS analysis of the culture media demonstrated mass insulin secretion by GLP-1-treated tumor cells.Metabolic profile changes in response to GLP-1-induced cell differentiation include selective increases in de novo fatty acid synthesis from glucose and consequent chain elongation, allowing increased membrane formation and greater insulin availability and release.

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Bacteroidaceae are common gut microbiota members in all warm-blooded animals. However, if Bacteroidaceae are to be used as probiotics, the species selected for different hosts should reflect the natural distribution. In this study, we therefore evaluated host adaptation of bacterial species belonging to the family Bacteroidaceae. B. dorei, B. uniformis, B. xylanisolvens, B. ovatus, B. clarus, B. thetaiotaomicron and B. vulgatus represented human-adapted species while B. gallinaceum, B. caecigallinarum, B. mediterraneensis, B. caecicola, M. massiliensis, B. plebeius and B. coprocola were commonly detected in chicken but not human gut microbiota. There were 29 genes which were present in all human-adapted Bacteroides but absent from the genomes of all chicken isolates, and these included genes required for the pentose cycle and glutamate or histidine metabolism. These genes were expressed during an in vitro competitive assay, in which human-adapted Bacteroides species overgrew the chicken-adapted isolates. Not a single gene specific for the chicken-adapted species was found. Instead, chicken-adapted species exhibited signs of frequent horizontal gene transfer, of KUP, linA and sugE genes in particular. The differences in host adaptation should be considered when the new generation of probiotics for humans or chickens is designed. [ABSTRACT FROM AUTHOR]