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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]

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.

The effects of hydroquinone (200 mg/kg) on spontaneous periodic motor activity (SPMA) and a number of biochemical markers were studied in 116-day-old rats. According to Laborit (1965), the mechanism of hydroquinone action is based on inhibition of the pentose phosphate pathway in excitable structures. Herein, we confirmed that intraperitoneal injection of hydroquinone drastically changes the SPMA pattern, inducing uninterrupted intense motor activity. To test the metabolic, redox and anticholinergic hypotheses, various feasible targets of hydroquinone were addressed. The experimental results revealed age-related changes in a number of biochemical markers. In erythrocytes (RBC), hydroquinone induced a slight increase in lactate and pyruvate levels but did not affect the glucose level, nor did it inhibit the activity of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PDH) in vitro. Hydroquinone did not affect significantly RBS levels of reduced and oxidised glutathione (GSH and GSSG) and different types of hemoglobin as well as plasma levels of malonic dialdehyde (MDA). High doses of hydroquinone inhibited RBC acetylcholinesterase (AChE) in vitro. However, blockade of central and peripheral muscarinic and nicotinic acetylcholine receptors, induced both before and after hydroquinone injection, did not prevent SPMA potentiation and changes in its pattern. Thus, our results cast doubt both on the metabolic hypothesis of the hydroquinone action and the physiological relevance of its anticholinesterase effect to enhancing motor activity. The tasks for further investigation in this direction are outlined. [ABSTRACT FROM AUTHOR]

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]