Restructuring Of Metabolism Research Articles

The influence of cancer on the reprogramming of lipid metabolism in healthy thyroid tissues of patients with papillary thyroid carcinoma.

Over the years we observed changes in the metabolism of glucose, amino acids, fatty acids (FA) and nucleotides in cancer cells in order to maintain their viability and proliferate. Moreover, as the latest data show, cancer also forces a complete change in the behavior of other tissues. For instance, fat-filled adipocytes are often found in the vicinity of invasive solid human tumors. We investigated the effects of papillary thyroid carcinoma (PTC) on the lipid metabolism of healthy tissue distant from the tumor. Thyroid tissue was collected from female patients immediately after surgical removal of the entire thyroid gland. Blood samples were collected from PTC patients and healthy volunteers. Real-time PCR assays were performed to analyze the expression of lipogenic genes and a broad panel of FA was determined using the gas chromatography-mass spectrometry method. The concentration of lipids was higher in paratumor tissue than in healthy thyroid tissue (p = 0.005). The lipogenic genes tested were significantly increased in paratumor tissue compared to healthy tissue, especially enzymes related to the synthesis of very long-chain saturated and polyunsaturated FAs (VLCSFAs and PUFAs, respectively) (p < 0.001). The FA profile also showed increased levels of C22-C26, VLCSFAs and almost all PUFAs in paratumor tissue (p < 0.05). Our study suggests that a restructuring of lipid metabolism occurs in the adjacent healthy thyroid gland and that the metabolism of VLCSFAs and PUFAs is higher in the paratumor tissue than in the distant tissue of the healthy thyroid gland.

Mammal hibernation as a strategy for adaptation to unfavorable environmental conditions

To analyse the literature data on the survival pathways of heterothermic endotherms in unfavorable environmental conditions, during periods of low availability of food resources.The article provides data on the differences between daily and seasonal heterothermy. The features of preparation for hibernation in facultative and obligate hibernators are highlighted. Hypotheses of the origin and evolution of heterothermy are considered. The most probable causes of periodic awakenings of animals from hibernation during the hibernation period are summarised. Considerable attention is paid to the restructuring of energy metabolism during hibernation – the transition from carbohydrate to lipid metabolism. Data have been analysed indicating the importance of fatty acids obtained from food during the active summer period, both for the synthesis of reserve fats and in the regulation of hibernation. Based on data on the accumulation of monoenoic fatty acids in tissues during hibernation, it has been suggested that they have an adaptive significance aimed at limiting oxidative stress and preserving vital cell functions.The data presented can be used both for conducting fundamental research on the adaptive mechanisms of interaction of an organism with its environment, and for solving practical problems, especially when choosing models of calorie restriction or intermittent fasting, as well as studying tissue tolerance to oxidative stress and resistance to the damaging effects of ischemia – reperfusion.

LIPID METABOLISM INDICATORS IN SOW BLOOD UNDER THE INFLUENCE OF IRON AND GERMANIUM NANOCOMPOUNDS

The relevance of the conducted research is determined by the lack of information in the available literature regarding the influence of iron and germanium nanoparticles on lipid exchange indicators in the plasma of sows. The aim of the study was to determine the effect of administering iron and germanium nanoparticles on lipid exchange indicators in the blood of sows before and after farrowing. The experiment was conducted on 24 large white sows, aged 2-3 years, which were divided into two groups (control and experimental). For ten days before farrowing, the sows in the experimental group were administered a complex of micronutrient compounds of iron – 3 mg/day and germanium – 0.01 mg/day. Blood plasma of the animals was used as material for the study, in which specific lipid exchange indicators were determined. The effect of farrowing on the content of triacylglycerols, non-esterified fatty acids, and total cholesterol in the blood plasma of animals was established (F= 33.0–156.0 &gt; FU=2.9; P &lt; 0.001). Before farrowing, there is a restructuring of lipid metabolism in sows, characterized by a decrease in the content of triacylglycerols and total cholesterol, and an increase in the content of non-esterified fatty acids in the blood plasma. It was found that within a day before farrowing, the content of triacylglycerols decreases by 30.6% (P≤0.001), total cholesterol by 18.3% (P≤0.01), and non-esterified fatty acids increase by 1.5 times (P≤0.001). Administering iron and germanium nanoparticles significantly affects the content of triacylglycerols (η²ᵪ=0.53; P≤0.05), total cholesterol (η²ᵪ=0.69; P≤0.01), and non-esterified fatty acids (η²ᵪ=0.50; P≤0.05) in the blood plasma of sows only on the day of farrowing. During this time, in the blood of sows administered metal nanoparticles, the content of triacylglycerols and total cholesterol is higher by 23.7% (P≤0.05) and 11.5% (P≤0.01), respectively, and the content of non-esterified fatty acids is lower by 9.2% (P≤0.05) compared to the indicators of animals in the control group. The prospects for further research lie in the development of modern methods to increase the productivity and resistance of sows using metal nanoparticles.

Adaptive restructuring of grape metabolism in winter period

In the unstable conditions of the Anapo-Taman zone of the Krasnodar Krai, the urgency of the problem of winter hardiness of grapes increases due to an increase in the average annual air temperature against the background of an increase in the frequency of low critical air temperatures in the winter. The adaptive rearrangements of grape metabolism associated with resistance to winter stresses have been studied. Objects of research: grape varieties of different ecological and geographical origin: Crystal, Dostoyny, Krasnostop AZOS, Vostorg, Aligote, Zarif. The electrophoretic separation of peroxidases in polyacrylamide gel in the studied grape varieties revealed that the quantitative and qualitative composition of isoforms changed during the winter period and depended on the variety and the influence of the stress factor. During the autumn-winter period, the varieties Crystal, Krasnostop AZOS, Vostorg revealed an increased total content of anthocyanins in (13.2-14.4 conventional units), ascorbic acid in shoots (13.7-18.4 µg/g of raw weight) in contrast to the varieties Aligote, Zarif. According to the research, it was found that the Crystal grape variety has increased frost resistance, followed in descending order by Krasnostop AZOS, Vostorg, Dostoyny. These varieties have great adaptive capabilities in unstable conditions of a changing climate and are recommended for cultivation in the Anapo-Taman zone, as well as for use in breeding as sources of frost resistance. Varieties Aligote, Zarif are singled out as less frost-resistant.

Mechanotransduction signaling pathways of erythrocytes associated with restructuring of cell metabolism

Erythrocytes exhibit the properties of "sensor" of mechanical tension, hypoxia and "regulator" of vascular tone. In the in vivo bloodstream, these cells are constantly exposed to flow during which they experience varying levels of shear stress and strain. In this regard, these cells have well-established signaling mechanisms, with the participation of which a chemical response to a stress factor is formed. Vibration is a factor that, depending on its own physical characteristics, combines mechanical influence with an oxidative state or hypoxia. Thus, it was of interest to investigate how erythrocytes use certain signaling pathways to maintain metabolic homeostasis under the influence of low-frequency vibration. The paper examines the effect of vibration (frequency range 8–32 Hz, amplitudes 0.50 ± 0.04 and 0.90 ± 0.08 mm) on the energy state of human erythrocytes in the absence of glucose. In this connection, the changes of intracellular ATP, 2,3-BPG and inorganic phosphate (Pi) in human erythrocytes during 3-hour vibration exposure were investigated. The activity of Na+,K+-ATPase was investigated as an indicator reflecting cellular needs for ATP. Cytosolic 5’-nucleotidase (cN-1A) and AMP-deaminase (AMPDA) activities were investigated as indicators of the level of catabolism of purine nucleotides. To assess the involvement of adenosine in the processes of reverse signaling through the ADORA2B – AMPK BPGM axis, the activity of ectonucleotidase (eN) was investigated. Based on the obtained experimental data, an analysis of the signal mechanisms involved in the mechanotransduction of the vibration effect was carried out. It is shown that under certain conditions of vibration exposure (frequency interval 20–32 Hz, A = 0.50 ± 0.04 mm and 12–32 Hz, A = 0.90 ± 0.08 mm) erythrocytes use signaling and metabolic pathways aimed at increasing the content of ATP, 2,3-BPG and restoration of the energy charge of cells. One of these pathways is controlled by AMP-kinase (AMPK), which in turn is a participant in the signaling cascade that begins with adenosine receptors ADORA2B. AMPK turns off consumption pathways and turns on alternative pathways for ATP regeneration and activation of 2,3-BPG formation mechanisms. These ways are aimed at overcoming the state of hypoxia. Experimental data on the participation of AMP catabolism enzymes in ATP recovery processes were analyzed.

Serum Activity of Proteolytic Enzyme Trypsin in Rats under Conditions of Water and Food Deprivation.

Trypsin is mainly regarded as a digestive enzyme, but there is evidence that activation of protease-activated receptor-2 (PAR-2) leads to behavioral changes. There are no data on trypsin activity in the serum of animals under conditions of thirst and starvation in the available literature. In our experiments, water deprivation led to a significant (p⩽0.05) increase in trypsin activity in rats, and food deprivation led to its decrease in comparison with controls (free access to water and food). After deprived rats received water and food, a decrease in trypsin activity was observed in both experimental groups. Changes in trypsin activity under conditions of water or food deprivation and after satiation were accompanied by shifts in some biochemical parameters of the bloods. Under conditions of metabolic stress (starvation and thirst), opposite changes in trypsin activity seem to indicate its participation in the mechanisms of adequate restructuring of metabolism and maintenance of vital processes in the body.

Metabolic Regulation of Copper Toxicity during Marine Mussel Embryogenesis.

The development of new tools for assessing the health of cultured shellfish larvae is crucial for aquaculture industries to develop and refine hatchery methodologies. We established a large-volume ecotoxicology/health stressor trial, exposing mussel (Perna canaliculus) embryos to copper in the presence of ethylenediaminetetraacetic acid (EDTA). GC/MS-based metabolomics was applied to identify potential biomarkers for monitoring embryonic/larval health and to characterise mechanisms of metal toxicity. Cellular viability, developmental abnormalities, larval behaviour, mortality, and a targeted analysis of proteins involved in the regulation of reactive oxygen species were simultaneously evaluated to provide a complementary framework for interpretative purposes and authenticate the metabolomics data. Trace metal analysis and speciation modelling verified EDTA as an effective copper chelator. Toxicity thresholds for P. canaliculus were low, with 10% developmental abnormalities in D-stage larvae being recorded upon exposure to 1.10 μg·L-1 bioavailable copper for 66 h. Sublethal levels of bioavailable copper (0.04 and 1.10 μg·L-1) caused coordinated fluctuations in metabolite profiles, which were dependent on development stage, treatment level, and exposure duration. Larvae appeared to successfully employ various mechanisms involving the biosynthesis of antioxidants and a restructuring of energy-related metabolism to alleviate the toxic effects of copper on cells and developing tissues. These results suggest that regulation of trace metal-induced toxicity is tightly linked with metabolism during the early ontogenic development of marine mussels. Lethal-level bioavailable copper (50.3 μg·L-1) caused severe metabolic dysregulation after 3 h of exposure, which worsened with time, substantially delayed embryonic development, induced critical oxidative damage, initiated the apoptotic pathway, and resulted in cell/organism death shortly after 18 h of exposure. Metabolite profiling is a useful approach to (1) assess the health status of marine invertebrate embryos and larvae, (2) detect early warning biomarkers for trace metal contamination, and (3) identify novel regulatory mechanisms of copper-induced toxicity.

Amino acid composition of species of the genus Atriplex L. growing in the Aral Sea (Uzbekistan)

The largest number of plant cover species on saline soils of Uzbekistan belongs to the family Chenopodiaceae Vent. Plant origin is a promising and accessible source for isolating substances containing amino acids. In this regard, we conducted studies on the study of the amino acid and elemental composition of Atriplex aucheri Moq. plants and Atriplex tatarica L. The ability to withstand the type of stress factors is necessary and survival in this environment requires a profound restructuring of plant metabolism, photosynthesis and transpiration, as well as the biosynthesis of adaptogenic substances. Therefore, these plants are potential candidates for the creation of new biologically active substances, stress-protective combinations of macro and microelements, which may be promising for further biotechnological, agricultural and biomedical use. As a result of the analysis, 20 free amino acids were identified in the studied species of the genus Atriplex, of which 10 are essential - threonine, arginine, valine, methionine, isoleucine, histidine, tryptophan, phenylalanine, lysine, leucine. Comparison of the content of amino acids showed that the amount of methionine was the highest in both species.

Лактатдегидрогеназа в условиях фармакологической блокады симпатического ганглия

The isoenzymes activity of LDH in the cranial cervical sympathetic ganglion (SCG) of rabbits was determined by disc- electrophoresis under conditions of pharmacological ganglion blockade by subcutaneous administration of the cholinolytic dimecoline. Pharmacological blockade causes significant rearrangements of the LDH isoenzyme spectrum in SCG. There is a complete reduction of M isoforms (LDH-4 and -5), H isoforms (LDH-1 and -2) only remain. It is assumed that a decrease in the activity of all LDH isoforms during pharmacological blockade occurs by allosteric inhibition and leads to a significant restructuring of metabolism and to hypofunction of SCG.

Diabetes mellitus — metabolic preconditioning in protecting the heart from ischemic damage?

The negative impact of diabetes mellitus (DM) on the cardiovascular system has been confirmed by numerous clinical studies. However, there are experimental studies that show an increase in the resistance of the heart to ischemic and reperfusion damage in animals with DM. This phenomenon is characterized by a smaller size of the infarct zone, better preservation of the contractile function of the myocardium, and a lower incidence of ischemic and reperfusion arrhythmias. It is assumed that at a certain stage in the development of DM, a “metabolic window” is formed, in which metabolic alterations at the cellular level trigger adaptive mechanisms that increase the viability of cardiomyocytes. Published data confirm that the magnitude of the protective effect induced by DM is comparable to, and in some cases even exceeds, the effect of the preconditioning phenomenon. It is recognized that the mechanisms that protect the heart from ischemic and reperfusion damage against the background of DM are universal and are associated with the modulation of the antioxidant system, apoptosis factors, pro-inflammatory cytokines, and signaling systems that ensure cell survival. The one of the main pathogenic factor in DM is hyperglycemia, but under stress it plays the role of an adaptive mechanism aimed at meeting the increased energy demand in pathological conditions. Probably, at a certain stage of DM, hyperglycemia becomes a trigger for the development of protective effects and activates not only signaling pathways, but also the restructuring of energy metabolism, which makes it possible to maintain ATP production at a sufficient level to maintain the vital activity of heart cells under ischemia/reperfusion conditions. It is possible that an increased level of glucose, accompanied by the activation of insulin-independent mechanisms of its entry into cells, as well as the availability of this energy substrate, will contribute to a better restoration of energy production in heart cells after a infarction, which, in turn, will significantly reduce the degree of myocardial damage and will help preserve the contractile function of the heart. Identification of the conditions and mechanisms of the cardioprotective phenomenon induced by DM will make it possible to simulate the metabolic state in which the protection of cardiomyocytes from damaging factors is realized.

Neuroprotective effect of mildronate and L-carnitine on the cognitive parameters of aged mice and mice with LPS-induced inflammation.

Mildronate (MD) is a cardioprotective drug used for the treatment of cardiovascular diseases by switching metabolism from the fatty acids to glucose oxidation. This effect is achieved via inhibition of synthesis of L-carnitine (L-car), a common supplement, which is used for improving of fatty acid metabolism. Both MD and L-car have similar neuroprotective effect. Our goal was to investigate the effect of two drugs on the cognitive parameters of mice under different conditions (aging and lipopolysaccharide (LPS)-induced inflammation). We showed that L-car partly improved the memory and decreased the extent of mtDNA damage in the hippocampus of mice with the LPS-induced inflammation. L-car induced mitochondrial biogenesis and mitophagy in the Nrf2-dependent manner. Both MD and L-car upregulated expression of genes involved in the mitochondrial quality control. In 15-month-old mice, MD improved long-term and short-term memory, reduced the extent of mtDNA damage, and decreased the concentration of diene conjugates in the hippocampus in the Nrf2-independent manner. L-car as a Nrf2 activator had a better neuroprotective effect by normalizing mitochondrial quality control in the reversible cognitive impairment caused by the LPS-induced inflammation, while MD had a better neuroprotective effect in the irreversible cognitive impairment in aged mice, possibly due to a deeper restructuring of metabolism and reduction of oxidative stress.

Oxidative stress and changes in liver sialoglycoconjugate metabolic parameters in rats with alloxanic diabetes mellitus

BACKGROUND: Oxidative stress may be one of the mechanisms for the development of complications in DM and many forms of CKD. However, the influence of this factor on the metabolism of sialoglycoconjugates, which actively participates in the regulatory processes of the body, is unknown.AIM: comparative study of the effect of lipoic acid on the parameters of liver sialoglycoconjugate metabolism in rats with alloxan diabetes mellitus.MATERIALS AND METHODS: Studies were conducted on white male rats weighing 180–220 grams. The animals were divided into three groups: in the animals of the first and second groups, alloxan diabetes mellitus (DM) was caused by a single subcutaneous injection of alloxan tetrahydrate (AT). Animals of the second group received lipoic acid intramuscularly; the third group consisted of intact rats. On 5, 10, 20, 30 and 40 days after the injection of AT, a comprehensive examination of the animal’s condition was performed: 1) determination of the level of glycemia; 2) assessment of the degree of development of oxidative stress by the content of TBK-active products in the liver; 3) study of the dynamics of the exchange of sialoglycoconjugates in the liver (free, oligo-and protein-bound sialic acids, sialidase activity).RESULTS: The study was conducted on 106 rats, each experimental group had 48 animals, control — 10. It was found that the administration of α-lipoic acid to rats with alloxan diabetes leads to a decrease in the level of glycemia. The introduction of lipoic acid in experimental animals did not reduce the sialidase activity and the content of all sialic acid fractions in the liver, although it reduced the degree of oxidative stress in the body.CONCLUSION: Supplementation of lipoic acid in experimental animals did not significantly decrease sialidase activity and content of the sialic acid fractions under study in the liver, although it did reduce the degree of oxidative stress development in the organism. The increased rate of sialic acid metabolism in the liver of alloxan-diabetic rats may indicate a restructuring of hepatocyte metabolism to adapt the whole organism to prolonged hyperglycemia under insulin deficiency conditions.

Contribution of stress granules and spliceosomal components to the formation of chemoresistance in ovarian cancer cells

The emergence of chemoresistance in cancer cells is one of the main reasons for the high mortality from oncological diseases. We have shown that signaling molecules from dying cancer cells contribute to a more aggressive therapy‐resistant phenotype. However, the molecular mechanisms underlying this effect remain elusive.Here we aimed to find out which proteins secreted by dying tumor cells get into recipient cells and to determine the molecular cascades triggered in response to incubation with therapy‐induced secretomes. We modified the SILAC (Stable Isotope Labeling by Amino acids in Cell culture) technology. A heavy‐labeled primary culture of ovarian cancer cells was treated or untreated with cisplatin for 48 h. Then using ultrafiltration cartridges, a fraction of extracellular vesicles (EV) were isolated from culture media. The obtained EV were resuspended in a medium containing Medium‐labeled amino acids and added to the recipient chemonaive unlabeled tumor cells for 24 h. During incubation, recipient cells absorbed EV with Heavy‐labeled proteins from donor cells and synthesized new proteins with Medium label. Then, we performed proteomic analysis of recipient cells. In total, we identified 4224 proteins. Interestingly, dying tumor cells secrete and recipient cells absorb a large number of spliceosomal and ribosomal proteins along with translation initiation complex. These proteins are often presented in stress granules. In response to EV from dying tumor cells, recipient cells upregulated the translation of genes responsible for the regulation of the cell cycle and oxidative phosphorylation.To our knowledge, this is the first report about the secretion of stress granules and spliceosomal components into the extracellular space and their internalization in other cells. To confirm these data we performed transfection of donor cells with constructs encoding the fluorescent proteins TIA1 (protein of stress granules) and SRSF4 (protein of the spliceosome). We showed that both proteins are re‐located together from the nucleus into the cytoplasm under the cisplatin treatment. Then, we demostrated the absorption of fluorescent‐labeled proteins TIA1 and SRSF4 by recipient cells after incubation with therapy‐induced EV. Our findings demonstrate that in response to cisplatin treatment tumor cells secrete spliceosomal components into the extracellular space (presumably as a part of stress granules), then these components are absorbed by recipient chemonaive cells and trigger a restructuring of metabolism and cell cycle.

АДАПТОГЕННОЕ ДЕЙСТВИЕ ПРЕПАРАТОВ АПИСИЛ И ТОС-БИО НА МЕДОНОСНУЮ ПЧЕЛУ В УСЛОВИЯХ ГИПЕРТЕРМИИ

The temperature factor has a huge impact on bees and their development. In a complex complex of adaptation, not only a perfect system of collective thermoregulation of the family is important, but also such individual adaptations as resistance to freezing and tolerance to high temperatures. The deviation of the ambient temperature from the optimal one increases the energy consumption of bees for the regulation of the microclimate in the family. This means that it enhances metabolic processes, which affects the state of the body and the life expectancy of insects. In addition, sometimes the use of high temperatures is a necessary condition for their maintenance, for example, in the fight against the parasite of the bee mite varroa. At the same time, the effect of high temperatures can have a negative effect not only on the mite, but also on the bees. In laboratory conditions, the effect of Apisil and TOS-BIO preparations containing 9-oxoand 10-hydroxy-2E-decenoic acids as a base - the most important components of the «queen substance» and royal jelly of the honey bee Apis mellifera L., respectively - on the survival rate and biochemical parameters was studied. adult worker bees exposed to extremely high (50oC) temperatures. The dynamics of the activity of phenoloxidase and catalase as biochemical indicators of the stress response of a honey bee under high temperature load has been studied. It was shown that the insects' resistance to hyperthermia increased with the content of these preparations in the feed. Experimental results indicate that under extreme (50oC) temperature conditions Apisil and TOS-BIO preparations have an adaptogenic effect on worker bees, increasing their resistance to hyperthermia. At the same time, changes in the initial level and dynamics of biochemical parameters indicate that these compositions in the most economical way contribute to the restructuring of metabolism in the mode of optimal functioning, which affects the level of changes in enzyme activity (with less pronounced changes in activity). and also on the survival rate of bees at the end of the experiment.

Gregarine single-cell transcriptomics reveals differential mitochondrial remodeling and adaptation in apicomplexans

BackgroundApicomplexa is a diverse phylum comprising unicellular endobiotic animal parasites and contains some of the most well-studied microbial eukaryotes including the devastating human pathogens Plasmodium falciparum and Cryptosporidium hominis. In contrast, data on the invertebrate-infecting gregarines remains sparse and their evolutionary relationship to other apicomplexans remains obscure. Most apicomplexans retain a highly modified plastid, while their mitochondria remain metabolically conserved. Cryptosporidium spp. inhabit an anaerobic host-gut environment and represent the known exception, having completely lost their plastid while retaining an extremely reduced mitochondrion that has lost its genome. Recent advances in single-cell sequencing have enabled the first broad genome-scale explorations of gregarines, providing evidence of differential plastid retention throughout the group. However, little is known about the retention and metabolic capacity of gregarine mitochondria.ResultsHere, we sequenced transcriptomes from five species of gregarines isolated from cockroaches. We combined these data with those from other apicomplexans, performed detailed phylogenomic analyses, and characterized their mitochondrial metabolism. Our results support the placement of Cryptosporidium as the earliest diverging lineage of apicomplexans, which impacts our interpretation of evolutionary events within the phylum. By mapping in silico predictions of core mitochondrial pathways onto our phylogeny, we identified convergently reduced mitochondria. These data show that the electron transport chain has been independently lost three times across the phylum, twice within gregarines.ConclusionsApicomplexan lineages show variable functional restructuring of mitochondrial metabolism that appears to have been driven by adaptations to parasitism and anaerobiosis. Our findings indicate that apicomplexans are rife with convergent adaptations, with shared features including morphology, energy metabolism, and intracellularity.

Microbial nutrient factories in insects on extreme diets

Insects are renowned for their capacity to specialize on a wide diversity of diets, many of which are nutrient-poor or nutritionally unbalanced. For example, various insects feed through the life cycle on wood, vertebrate blood, plant sap and other extreme diets that are variously deficient in vitamins, sterols and essential amino acids. These insects circumvent the fundamental “rules” of animal nutrition because they possess symbiotic microorganisms that overproduce the limiting dietary nutrients. Many associations between insects and microorganisms are evolutionarily ancient and involve the exquisite coevolution of metabolic function in the insect and microbial partners, including the restructuring of microbial metabolism as nutrient factories for the host ( Fig. 1 ). These insects include major pests and vectors of animal, human and crop disease agents. Their dependence on specific microorganisms offers novel routes for the control of these globally important insect pests.

Metabolism Is a Key Regulator of Induced Pluripotent Stem Cell Reprogramming.

Reprogramming to pluripotency involves drastic restructuring of both metabolism and the epigenome. However, induced pluripotent stem cells (iPSC) retain transcriptional memory, epigenetic memory, and metabolic memory from their somatic cells of origin and acquire aberrant characteristics distinct from either other pluripotent cells or parental cells, reflecting incomplete reprogramming. As a critical link between the microenvironment and regulation of the epigenome, nutrient availability likely plays a significant role in the retention of somatic cell memory by iPSC. Significantly, relative nutrient availability impacts iPSC reprogramming efficiency, epigenetic regulation and cell fate, and differentially alters their ability to respond to physiological stimuli. The significance of metabolites during the reprogramming process is central to further elucidating how iPSC retain somatic cell characteristics and optimising culture conditions to generate iPSC with physiological phenotypes to ensure their reliable use in basic research and clinical applications. This review serves to integrate studies on iPSC reprogramming, memory retention and metabolism, and identifies areas in which current knowledge is limited.

Metabolism and Physiological Functions Adjustment of the Organism under Stress Influence

Stress reaction of the organism is a process occurring at the cellular, tissue and systemic levels. The organism responds to any adverse effect with a multi-level reaction, which causes the development of stress and, as a result, adaptation. The damaging effect is due to the excessive strengthening of another adaptive effect – lipotropic, that increases the activity of phospholipases and the intensity of free radical oxidation of lipids through the catecholamines and protein kinases. The changes in the immune system during the adaptation stage are to maintain antigenic homeostasis of the internal environment of the organism due to lymphoid cells, lymphocytes and cytokines. Almost all cells with antigen representation function are capable to produce interleukins under certain conditions. The vascular system is a kind of an indicator of any pathological process, determining the state of regulatory and adaptive mechanisms, the features of the connective tissue matrix. Stress causes a restructuring of metabolism and physiological functions, which increases the organism’s resistance to acute death. Thus, the physiological meaning of the stress reaction is the emergency mobilization of energy and structural resources of the organism and the creation of positive background for the implementation of reactions, aimed at maintaining homeostasis in extreme situations.

Blood lipids in athletes depending on the orientation of the training process

Sports form the metabolic response caused by the body’s adaptation to increased physical stress, which leads to the restructuring of metabolism for energy and plastic maintenance of sport activities. The restructuring of carbohydrate and lipid metabolism is caused primarily by the increasing energy request body, depending on type and intensity of sports activity. In this research blood serum lipids were studied depending on the orientation of the training process. A total of 108 athletes (men and women) aged 15 to 20 years of different sports qualification (I sports category, Candidate Master of Sports and Master of Sports) were examined, and a control group of 28 persons of the same age and gender. Depending of the direction of the training process there were isolated 3 groups: cyclical sport that develops mainly endurance (academic rowing); sports of complex nature (football, volleyball, handball and Nordic combined); and complex coordinated sports (artistic gymnastics). Were studied: total cholesterol, high density lipoproteins, low-density lipoproteins, atherogenic coefficient and triglycerides. The study was conducted in the preparatory period of the training cycle. The research had shown that the level of blood lipids depends on the orientation of training process and sports training. The most marked reduction of total cholesterol and high-density lipoproteins has been observed both in men and women in cyclic kinds of sports, developing mainly stamina that indicates that intense exercise in athletes who train primarily for endurance, cause the connection of lipids to the processes of energy supply of muscle activity.

Elucidating the role of copper in CHO cell energy metabolism using (13)C metabolic flux analysis.

(13)C-metabolic flux analysis was used to understand copper deficiency-related restructuring of energy metabolism, which leads to excessive lactate production in recombinant protein-producing CHO cells. Stationary-phase labeling experiments with U-(13)C glucose were conducted on CHO cells grown under high and limiting copper in 3 L fed-batch bioreactors. The resultant labeling patterns of soluble metabolites were measured by GC-MS and used to estimate metabolic fluxes in the central carbon metabolism pathways using OpenFlux. Fluxes were evaluated 300 times from stoichiometrically feasible random guess values and their confidence intervals calculated by Monte Carlo simulations. Results from metabolic flux analysis exhibited significant carbon redistribution throughout the metabolic network in cells under Cu deficiency. Specifically, glycolytic fluxes increased (25%-79% relative to glucose uptake) whereas fluxes through the TCA and pentose phosphate pathway (PPP) were lower (15%-23% and 74%, respectively) compared with the Cu-containing condition. Furthermore, under Cu deficiency, 33% of the flux entering TCA via the pyruvate node was redirected to lactate and malate production. Based on these results, we hypothesize that Cu deficiency disrupts the electron transport chain causing ATP deficiency, redox imbalance, and oxidative stress, which in turn drive copper-deficient CHO cells to produce energy via aerobic glycolysis, which is associated with excessive lactate production, rather than the more efficient route of oxidative phosphorylation.