Pyruvate Levels Research Articles

Effects of 2-ethylhexyl diphenyl phosphate exposure on the glucolipid metabolism and cardiac developmental toxicity in larval zebrafish based on transcriptomic analysis

2-Ethylhexyl diphenyl phosphate (EHDPP) is an organophosphorus type of flame retardant. It is mainly used as a flame-retardant plasticizer in the production of flexible polyvinyl chloride. EHDPP is widely present in environment, particularly in aquatic environment. In this study, we reported that EHDPP exposure significantly affected glucose and lipid metabolism in zebrafish larvae, which was reflected by changes in the transcription of relevant genes and decreased levels of glucose, pyruvate, and triglycerides. In addition, the transcriptomic analysis revealed that the differentially expressed genes could enrich various endpoints in zebrafish larvae. Interestingly, EHDPP exposure could not only change the transcription of genes related to glucolipid metabolism but also cause cardiotoxicity by affecting the transcription of genes related to calcium signaling pathways in zebrafish larvae. To support these findings, we confirmed that these genes involved in cardiac morphology and development were significantly upregulated in zebrafish larvae after EHDPP exposure. More importantly, the distance and overlapping area of the atrium and ventricle were also changed in the EHDPP-exposed zebrafish larvae of transgenic Tg (myl7: EGFP). Overall, our study revealed that EHDPP exposure could affect various endpoints related to glucolipid metabolism and cardiac development in the early developmental stages of zebrafish.

Maltol inhibits oxygen glucose deprivation‑induced chromatinolysis in SH‑SY5Y cells by maintaining pyruvate level.

Maltol, a chemical isolated from ginseng root, has shown treatment effects on several pathological processes including osteoarthritis, diabetic peripheral neuropathy and liver fibrosis. Nevertheless, its effect on ischemia‑induced neuron death remains elusive. In the present study, the treatment effect of maltol on ischemia‑induced neuron damage was investigated by using oxygen and glucose deprivation (OGD) model in SH‑SY5Y cells. Invitro studies revealed that maltol protected SH‑SY5Y cells against OGD‑induced chromatinolysis by inhibiting two reactive oxygen species (ROS)‑regulated pathways. One was DNA double‑strand breaks and the other was nuclear translocation of apoptosis inducing factor. Mechanistically, maltol not only inhibited OGD‑induced depletion of glutathione and cysteine by maintaining cystine/glutamate antiporter (xCT) level, but also abrogated OGD‑induced catalase downregulation. Meanwhile, maltol also alleviated OGD‑induced inactivation of mTOR by attenuating OGD‑induced depletion of adenosine triphosphate and pyruvate and downregulation of pyruvate kinase M2, indicating that maltol inhibited the glycolysis dysfunction caused by OGD. Considering that activated mammalian target of the rapamycin (mTOR) could lead to enhanced xCT expression and decreased catalase degradation by autophagy, these findings indicated that maltol attenuated OGD‑induced ROS via inhibition of mTOR inactivation by maintaining pyruvate level. Taken together, it was demonstrated that maltol prevented OGD‑induced chromatinolysis in SH‑SY5Y cells via inhibiting pyruvate depletion.

Resveratrol inhibits multiple organ injury in preeclampsia rat model.

To investigate the effects of resveratrol on multiple organ injury and energy metabolism and its possible mechanism in preeclampsia model. A total of 45 clean-grade female adults Sprague Dawley (SD) rats (weight 270-320 g) were randomly divided into three groups: a control group, preeclampsia group (PE), and Preeclampsia with resveratrol treatment group (RE). Preeclampsia was induced in rats by administering 200 mg/kg/day L-NAME. Expression levels of TNF-α and IL-6 in the lungs and kidney tissues were analysed by ELISA, while the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) was determined by biochemical assays. The levels of lactic acid and pyruvate were detected using biochemical assays, while the epinephrine level in the kidney and heart tissues was determined by the ELISA method. Reverse transcription polymerase chain reaction and the western blotting were used to detect the expression of pyruvate dehydrogenase kinase 4 (PDK4) in the myocardial tissues. We found that resveratrol treatment inhibited the levels of IL-6, TNF-α, and MDA in the lungs and kidney tissues, while the SOD activity was increased. Treatment with resveratrol reduced the levels of lactic acid, pyruvate, and epinephrine in the kidney and heart tissues. Furthermore, resveratrol treatment significantly increases the expression of PDK4 myocardial tissues in RE group compared to PE group. Resveratrol may inhibit the release of tissue inflammatory factors, regulate the body's energy metabolism, and ultimately protect tissue damage caused during Preeclampsia.

Short- and long-term cognitive and metabolic effects of medium-chain triglyceride supplementation in rats

Medium-chain triglycerides (MCT) possess neuroprotective properties. However, the long-term metabolic consequences of supplementing a regular diet with cognition-enhancing doses of MCT are largely unknown. We studied the effects of chronic (28 days) supplementation of regular diet with different doses of MCT oil (1, 3, or 6 g/kg/day) or water (control) on working memory (Y-maze), behavior in the Open Field, spatial learning (Morris water maze), and weight of internal organs in male Wistar 2.5-m.o. Rats. In a separate experiment, we evaluated acute (single gavage) and chronic (28 days) effects of MCT or lard supplementation (3 g/kg) on blood biochemical parameters. MCT-1 and MCT-3 doses improved working memory in YM. In MWM, MCT-6 treatment improved spatial memory. Chronic MCT-1 or MCT-3 treatment did not affect internal organ weight, while MCT-6 dose increased liver weight and the brown/white adipose tissue ratio. Acutely, MCT administration elevated blood β-hydroxybutyrate and malondialdehyde levels. Chronic MCT administration (3 g/kg) did not affect the blood levels of glucose, lactate, pyruvate, acetoacetate, β-hydroxybutyrate, total and HDL cholesterol, triglycerides, malondialdehyde, and aspartate transaminase and alanine transaminase activities. Therefore, daily supplementation of standard feed with MCT resulted in mild intermittent ketosis. It improved working memory at lower concentrations without significant adverse side effects. At higher concentrations, it improved long-term spatial memory but also resulted in organ weight changes and is likely unsafe. These results highlight the importance of monitoring the metabolic effects of MCT supplementation alongside cognitive assessment in future studies of MCT's neuroprotective properties.

Investigation of Energy Metabolism in The Different Tissues of Colon Cancer Xenograft Models Based on The TCA and Cori Cycles and Glycolysis

The metabolism is reprogrammed in cancer cells to meet the requirement of their malignant properties. Some specific metabolites can contribute to the malignant transformation in different cancer types. This study aimed to determine the level of glucose, pyruvate, lactate, citrate, alpha-ketoglutarate (α-KG), 2-hydroxyglutarate (2-HG), succinate, fumarate, malate, and oxaloacetate in the different tissues (tumor, colon, brain, and liver) of xenograft models generated by a colon adenocarcinoma cell line (SW480). Glucose and pyruvate levels were determined by the 3,5-dinitrosalicylic acid (DNS) method and pyruvate assay, respectively. The level of other metabolites was determined by the HPLC analysis. The results show that D-2-HG is highly produced in the tumor tissues (120.2 mg/L), but it could not be detected in liver tissue. In conclusion, TCA and Cori cycles and Glycolysis were investigated in the different tissues of colon cancer xenograft models and found that some metabolites produced tissue-specific.

Resveratrol regulates insulin resistance to improve the glycolytic pathway by activating SIRT2 in PCOS granulosa cells.

Insulin resistance (IR) has a close relationship with the main clinical manifestations of patients with PCOS; hence, the research and development of new drugs to treat PCOS by improving IR is a desiderate task at present. Resveratrol (RES) possesses a variety of beneficial pharmacological functions, such as antioxidation, anti-inflammatory, regulating glucose, and lipid metabolism. However, whether RES could improve IR and the underlying mechanisms remained unclear in PCOS. SD rats received a high-fat diet and letrozole for 30 days to establish the PCOS model and then intervened with RES for 30 days. The results demonstrated that RES played a protective role on the IR in PCOS rats, which significantly decreased the levels of blood glucose and serum insulin, up regulated the expression of IGF1R, and down regulated the expression of IGF1. In vitro, KGN cells were treated with insulin, RES, and AGK2, respectively. We found that a high dose of insulin (4μg/mL) significantly inhibited KGN cell viability, decreased the level of lactic acid, and increased the level of pyruvate, while RES (25μM) attenuated the growth-inhibitory effect, as well as increased the level of lactic acid and decreased the level of pyruvate after high levels of insulin treatment. Simultaneously, RES up regulated the expression level of the crucial rate-limiting enzymes relating to glycolytic pathways, such as LDHA, HK2, and PKM2. Furthermore, AGK2 remarkably inhibited the expression level of SIRT2, which was similar to the same negative effects processed by insulin. Meanwhile, RES overtly repaired the glycolysis process by reversing the levels of lactic acid and pyruvate, together with up regulating the expression level of LDHA, HK2, and PKM2, after AGK2 treatment. RES could effectively improve insulin resistance and restore the glycolysis pathway by regulating SIRT2, which may contribute to attenuating the ovarian damage of PCOS rats and provide a potential treatment for patients with PCOS.

Combined toxicity of acetamiprid and cadmium to larval zebrafish (Danio rerio) based on metabolomic analysis

Emerging contaminants, such as neonicotinoid pesticide acetamiprid (Ace), are frequently detected in the water environment, which can interact with existing heavy metal cadmium (Cd) to produce unpredicted influence. Limited studies have evaluated the effects of multiple pollutant exposures on aquatic animals. Here, we characterized the joint toxicity of Ace and Cd exposure to zebrafish (Danio rerio). The results revealed that Cd and its combined exposure with Ace had an inhibitory effect on the growth of larval zebrafish and induced morphological defects. Combined exposure to high doses of Ace and Cd could significantly reduce the levels of TG, glucose, and pyruvate in larval zebrafish. Untargeted metabolomics revealed that Cd treatment (285) produced more differentially expressed metabolites (DEMs) than Ace treatment (115), and combined treatment produced the most DEMs (294). The KEGG pathway enrichment analysis showed that they could disrupt riboflavin metabolism, amino acid metabolism, and glycolipid metabolism in the larvae of D. rerio. ELISA showed that VB2, FMN, and FAD levels were significantly increased. In addition, gene expression analysis exhibited that the mRNA levels of essential genes related to glycolipid metabolism were substantially affected, such as PK, PEPckc, PPAR-α, and FABP6. Furthermore, targeted amino acid metabolomics confirmed that both single exposure to Cd and combined exposure to Ace and Cd altered the levels of amino acids in larvae, including ALA, ARG, MET, PRO, TYR, VAL, GLY, ORN, and PHE. Taken together, exposure to Ace and Cd, alone or in combination, exerted harmful effects on the individual development, riboflavin metabolism, glycolipid metabolism, and amino acid metabolism disorder of D. rerio. These findings highlighted that more attention should be paid to the compound toxicity of chemical mixtures to aquatic organisms.

Wild-type IDH1 Knockout Leads to G0/G1 Arrest, Impairs Cancer Cell Proliferation, Altering Glycolysis, and the TCA Cycle in Colon Cancer.

The isocitrate dehydrogenase (IDH), which participates in the TCA cycle, is an important key enzyme in regulating cell metabolism. The effect of the metabolic IDH enzyme on cancer pathogenesis has recently been shown in different types of cancer. However, the role of wild-type (wt) IDH1 in the development of colon cancer is still unknown. Our study investigated the role of the IDH1 enzyme in key hallmarks of colon cancer using various methods such as wound healing, cell cycle, colony formation ability, invasion, and apoptosis analysis. Furthermore, cell metabolism was investigated by pyruvate analysis, dinitrosalicylic acid, and HPLC methods. In addition, CRISPR/Cas9 tool was utilized to knockout the IDH1 gene in colon adenocarcinoma cells (SW620). Further studies were performed in two isogenic IDH1 KO clones. Our findings in both clones suggest that IDH1 KO results in G0/G1 arrest, and reduces proliferation by approximately twofold compared to IDH1 WT cells. In addition, the invasion, migration, and colony formation abilities of IDH1 KO clones were significantly decreased accompanied by significant morphological changes. In the context of metabolism, intracellular glucose, pyruvate, αKG, and malate levels were decreased, while the intracellular citrate level was increased in IDH1 KO clones as compared to IDH1 WT cells. Our results reveal that wt IDH1 knockout leads to a decrease in the aggressive features of colon cancer cells. In conclusion, we reported that wt IDH1 has an effective role in colon cancer progression and could be a potential therapeutic target.

Dynamic correlation between tetramethylpyrazine and influencing factors in Bacillus subtilis-fermented dehulled adlay

Tetramethylpyrazine (TMP), a flavor compound with biological activity, naturally exists in a variety of roasted, fried or fermented foods. Biosynthesis has been green and effective practice to produce TMP, and high TMP level was obtained in Bacillus subtilis BJ3-2 fermented dehulled adlay (BDA) in previous study. To elucidate the correlation between TMP and influencing factors in this study, the dynamics of TMP and influencing factors in BDA were investigated, and the correlation between TMP and influencing factors was analyzed by Pearson's correlation coefficients. Results showed that a weakly acidic environment was found in BDA and B. subtilis CICC 20637 fermented dehulled adlay (CDA), but a weakly alkaline environment was observed in B. subtilis BJ3-2 fermented soybean (BSB). The higher levels of α-acetolactate decarboxylase, reducing sugar, pyruvate, diacetyl, leucine, acetoin and TMP were detected in BDA, while higher levels of α-acetolactate synthase, free amino acids and ammonium were obtained in BSB. At the end of fermentation, the TMP content in BDA was 6.13 mg/g dry weight, which was 204- and 12-fold higher than that in BSB and CDA, respectively. TMP synthesis in BDA and CDA was remarkable correlation with pyruvate, diacetyl, leucine, ammonium and acetoin (p < 0.05). In summary, a weakly acidic environment, moderate ammonium content, high leucine and acetoin levels synergistically promoted TMP efficient synthesis.

Glycolytic Plasticity of Metastatic Lung Cancer Captured by Noninvasive 18F-FDG PET/CT and Serum 1H-NMR Analysis: An Orthotopic Murine Model Study.

We aim to establish a noninvasive diagnostic platform to capture early phenotypic transformation for metastasis using 18F-FDG PET and 1H-NMR-based serum metabolomics. Mice with implantation of NCI-H460 cells grew only primary lung tumors in the localized group and had both primary and metastatic lung tumors in the metastatic group. The serum metabolites were analyzed using 1H-NMR at the time of PET/CT scan. The glycolysis status and cell proliferation were validated by Western blotting and staining. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of SUVmean and serum metabolites in metastasis. In the metastatic mice, the SUVmean of metastatic tumors was significantly higher than that of primary lung tumors in PET images, which was supported by elevated glycolytic protein expression of HK2 and PKM2. The serum pyruvate level in the metastatic group was significantly lower than that in the localized group, corresponding to increased pyruvate-catalyzed enzyme and proliferation rates in metastatic tumors. In diagnosing localized or metastatic tumors, the areas under the ROC curves of SUVmean and pyruvate were 0.92 and 0.91, respectively, with p < 0.05. In conclusion, the combination of 18F-FDG PET and 1H-NMR-based serum metabolomics demonstrated the feasibility of a glycolytic platform for diagnosing metastatic lung cancers.

Thiamine-responsive pyruvate dehydrogenase complex deficiency presenting as recurrent muscle weakness: Identification of a novel mutation (p.T111I) in the PDHA1 gene.

Thiamine-responsive pyruvate dehydrogenase complex deficiency presenting as recurrent muscle weakness: Identification of a novel mutation (p.T111I) in the PDHA1 gene.

Multi-parametric hyperpolarized 13C/1H imaging reveals Warburg-related metabolic dysfunction and associated regional heterogeneity in high-grade human gliomas

BackgroundDynamic hyperpolarized (HP)-13C MRI has enabled real-time, non-invasive assessment of Warburg-related metabolic dysregulation in glioma using a [1-13C]pyruvate tracer that undergoes conversion to [1-13C]lactate and [13C]bicarbonate. Using a multi-parametric 1H/HP-13C imaging approach, we investigated dynamic and steady-state metabolism, together with physiological parameters, in high-grade gliomas to characterize active tumor. MethodsMulti-parametric 1H/HP-13C MRI data were acquired from fifteen patients with progressive/treatment-naïve glioblastoma [prog/TN GBM, IDH-wildtype (n = 11)], progressive astrocytoma, IDH-mutant, grade 4 (G4AIDH+, n = 2) and GBM manifesting treatment effects (n = 2). Voxel-wise regional analysis of the cohort with prog/TN GBM assessed imaging heterogeneity across contrast-enhancing/non-enhancing lesions (CEL/NEL) and normal-appearing white matter (NAWM) using a mixed effects model. To enable cross-nucleus parameter association, normalized perfusion, diffusion, and dynamic/steady-state (HP-13C/spectroscopic) metabolic data were collectively examined at the 13C resolution. Prog/TN GBM were similarly compared against progressive G4AIDH+ and treatment effects. ResultsRegional analysis of Prog/TN GBM metabolism revealed statistically significant heterogeneity in 1H choline-to-N-acetylaspartate index (CNI)max, [1-13C]lactate, modified [1-13C]lactate-to-[1-13C]pyruvate ratio (CELval > NELval > NAWMval); [1-13C]lactate-to-[13C]bicarbonate ratio (CELval > NELval/NAWMval); and 1H-lactate (CELval/NELval > NAWMundetected). Significant associations were found between normalized perfusion (cerebral blood volume, nCBV; peak height, nPH) and levels of [1-13C]pyruvate and [1-13C]lactate, as well as between CNImax and levels of [1-13C]pyruvate, [1-13C]lactate and modified ratio. GBM, by comparison to G4AIDH+, displayed lower perfusion %-recovery and modeled rate constants for [1-13C]pyruvate-to-[1-13C]lactate conversion (kPL), and higher 1H-lactate and [1-13C]pyruvate levels, while having higher nCBV, %-recovery, kPL, [1-13C]pyruvate-to-[1-13C]lactate and modified ratios relative to treatment effects. ConclusionsGBM consistently displayed aberrant, Warburg-related metabolism and regional heterogeneity detectable by novel HP-13C/1H imaging techniques.

Metabolite variations in the sera of HIV+ patients after an oral administration of effervescent glutamine and in comparison to non-HIV individuals by NMR.

It was demonstrated that effervescent glutamine supplementation in HIV+ individuals treated with antiretroviral therapy (ART) increased CD4+ T lymphocytes, decreased inflammation biomarkers, and brought health benefits. This pilot study aimed to explore serum metabolite variations in the HIV+ group under ART after 30 days of supplementation with glutamine, and in comparison to the matched HIV- group. The group of HIV+ showed lower levels of choline, creatine, pyruvate, glutamate, lysine, and tyrosine when compared to the HIV- group. Glucose, lipids, lactate, glutamine, phenylalanine, threonine, and phenylalanine/tyrosine were higher in HIV+ patients under long ART. Serum metabolome variations were shown to be consistent with the health improvements observed in the HIV+ group after effervescent glutamine supplementation, which might aid in ART in HIV+ individuals.

PS-B12-4: SOLUBLE (PRO)RENIN RECEPTOR LEVEL INCREASED IN A RAT MODEL OF REDUCED UTERINE PERFUSION PRESSURE

Objective: The (pro)renin receptor [(P)RR)] is a multifunctional protein with roles in angiotensin II-dependent and -independent intracellular cell signaling and as an adaptor protein between the Wnt receptor complex and vacuolar proton-translocating adenosine triphosphatase. The (P)RR is cleaved from the full length (P)RR to generate soluble (P)RR [s(P)RR], reflecting the status of the tissue activity of the (P)RR. We have shown that maternal blood s(P)RR concentrations in early pregnancy are associated with increased blood pressure in late pregnancy, while higher levels of s(P)RR in cord blood in babies are at lower risk of low birth weight. We have also reported that intracellular s(P)RR is increased by hypoxia and interacts with pyruvate dehydrogenase β; subunit (PDHB) to stabilize PDHB protein and pyruvate dehydrogenase (PDH) activity in trophoblast cells, leading to our hypothesis that (P)RR may help maintain oxidative metabolism and efficient energy production during placental ischemia. In this in vivo study, we investigated effects of reduced uterine perfusion pressure (RUPP) on PDH activity and s(P)RR levels in rats. Design and method: RUPP was induced by placing sliver clips around the aorta above the iliac bifurcation and the bilateral uterine arcades in pregnant Sprague Dawley rats on gestational day 14 (RUPP rats). Weights of placentas and infants were measured on gestational day 21. mRNA expressions of (P)RR, hypoxia-inducible factor 1-alpha (HIF1a), and PDHB, and protein levels of HIF1a, (P)RR, s(P)RR, PDHB, lactate, and pyruvate, and activity of PDH in placentas were measured on gestational day 21. Result: Weight of placentas and infants were significantly decreased in RUPP rats when compared with those of sham rats. mRNA and protein levels of HIF1a were significantly higher in RUPP rats than in control sham rats, indicating that ischemia was actually induced by RUPP. mRNA levels of (P)RR and PDHB were not significantly different between the groups. The protein level of (P)RR was not significantly different between the groups while s(P)RR protein level was significantly higher in RUPP rats than in controls. Concentrations of lactate or pyruvate and PDH activity were not significantly different between the groups. Conclusion: PDH activity was not decreased even under the condition of placental ischemia. s(P)RR but not full length (P)RR was increased by placental ischemia. These data suggested that s(P)RR might be increased by placental ischemia to maintain mitochondrial oxidative metabolism in rats.

Quantification of pyruvate in-vitro using mid-infrared spectroscopy: Developing a system for microdialysis monitoring in traumatic brain injury patients

IntroductionComplex metabolic disruption is a major aspect of the pathophysiology of traumatic brain injury (TBI). Pyruvate is an intermediate in glucose metabolism and considered one of the most clinically informative metabolites during neurocritical care of TBI patients, especially in deducing the lactate/pyruvate ratio (LPR) – a widely-used metric for probing the brain's metabolic redox state. LPR is conventionally measured offline on a bedside analyzer, on hourly accumulations of brain microdialysate. However, there is increasing interest within the field to quantify microdialysate pyruvate and LPR continuously in near-real-time within its pathophysiological range. We have previously measured pure standard pyruvate in-vitro using mid-infrared transmission, employing a commercially available external cavity-quantum cascade laser (EC-QCL) and a microfluidic flow cell and reported a limit of detection (LOD) of 0.1 mM. Research questionThe present study was to test whether the current commercially available state-of-the-art mid-infrared transmission system, can detect pyruvate levels lower than previously reported. Materials and methodsWe measured pyruvate in perfusion fluid on the mid-infrared transmission system also equipped with an EC-QCL and microfluidic flow cells, tested at three pathlengths. ResultsWe characterised the system to extract its relevant figures-of-merit and report the LOD of 0.07 mM. Discussion and conclusionThe reported LOD of 0.07 mM represents a clinically recognised threshold and is the lowest value reported in the field for a sensor that can be coupled to microdialysis. While work is ongoing for a definitive evaluation of the system to measuring pyruvate, these preliminary results set a good benchmark and reference against which future developments can be examined.

CLINICAL PATHOGENETIC SUBSTANTIATION OF THE REGENERATIVE TREATMENT OF PARTURIENTS WHO SUFFERED FROM OBSTETRICAL HAEMORRHAGES

The publication is devoted to an urgent problem of modern obstetrics – the study of pathophysiological changes in the organism of parturients after obstetrical haemorrhages, improvement of restorative treatment, as well as reduction of complications in the puerperium and prevention of their occurrence. The aim of the study: to increase the effectiveness of restorative treatment of women in labor who suffered obstetric bleeding by studying the features of the clinical course, mechanisms of pathogenetic disorders, and their correction using ozone therapy. Materials and methods. A comprehensive clinical and laboratory examination of 150 women in labor was carried out, including 120 women (the main group) who suffered bleeding during childbirth and the early postpartum period. The control group consisted of 30 women with the physiological course of labor, childbirth and the early postpartum period. The state of lipid peroxidation (LPO) in parturient women was evaluated by the content of primary lipid products in the blood plasma – diene conjugates (DK) according to the method of B.V. Gavrilov (1983) and secondary molecular products – malondialdehyde (MDA) using the reaction with 2 thiobarbituric acid. The activity of the enzymatic link of the antioxidant system (AOS) was determined by the content of catalase in peripheral blood erythrocytes using the substrate hydrogen peroxide and glutathione peroxidase (GPO) using the P phenylenediamine substrate. The Spielberg–Hanin scale of state and trait anxiety was used to study the state of the psycho-emotional sphere in parturient women. Morphological examination of preparations of placentas and surgically removed uteri was carried out with staining of sections with hematoxylin and eosin, picrofuchsin according to Van Gieson. Results. Basic etiopathogenetic factors of the development of obstetric haemorrhages were examined, changes in the psychoemotional status of the patients were detected, haematological and metabolic indices, parameters of oxidation-antioxidation homeostasis and endogenic intoxication were studied, as well as morphofunctional disorders in placentas and uteruses. The efficacy of the restorative treatment of the parturients, who had moderate and massive haemorrhages during delivery, with the use of medical ozone in combined treatment versus traditional methods of treatment was studied. Conclusion. From the first day of the puerperium, free-radical lipid peroxidation increases, the activity of the enzymatic and non-enzymatic links of the antioxidant system increases, endogenous intoxication increases, and lactate and pyruvate levels increase. In the placentas of women in labor who suffered bleeding during labor, there is a violation of the synthesis of type IV collagen in the basal membranes of vessels and the phenomenon of endothelial dysfunction in the form of increased expression of endothelin by the endotheliocytes of the vessels of the decidual membrane (53.8 ± 2.9 µa) and the villous chorion (46.0 ± 2.6 μa). In the uterus, an increase in the expression of endothelin by endotheliocytes of the spiral arteries of the uterus (57.8 ± 8.56 µa) was detected, in combination with a violation of the synthesis of stromal collagen of type I and III and type IV in the basal membranes of vessels.

Cystic transformation of the pineal gland: clinical features and laboratory analysis of saliva and blood

Objective: to determine the content of melatonin and indicators of antihypoxic resistance, the state of antioxidant protection according to the determination of the level of lactate, pyruvate and indicators of the glutathione system (glutathione reductase and glutathione peroxidase) in patients with cystic transformation of the pineal gland (CSG).Materials and methods: during the period from January 2015 to December 2016, 5930 patients were examined, including 300 people with cystic transformation of the pineal gland. 56 people were selected for laboratory examination. The age of the examined patients ranged from 25 to 43 years. Of these, 37 people with cystic transformation of the pineal gland (CSG): 20 women — people, and men — 17 people, 19 people — the control group. The data obtained were considered both in relation to the general group of patients with this disease, and in relation to the division according to gender (men, women), and the volume of HTCW (“large”, “small”).Results: in the general group of patients, an increase in the content of melatonin in saliva and blood was recorded in all portions. Against this background, the aerobic direction of metabolism prevailed, the processes of consumption and restoration of reduced glutathione increased, which indicates the activation of the mechanisms of adaptive-compensatory restructuring of the functional state of the body.Conclusion: melatonin production in patients with cystic transformation of the pineal gland is correlated with the size of the cysts, with the most pronounced production being recorded at night. In women, to a greater extent than in men, signs of stimulation of oxygen-dependent processes are found, which indicates the intensity of adaptive reactions and the elimination of toxic products in response to stress associated with the presence of cysts.

Monochromatic Green Light Stimulation during Incubation Alters Hepatic Glucose Metabolism That Improves Embryonic Development in Yangzhou Goose Eggs

The influence of monochromatic green light stimulation on hatching performance and embryo development has been studied in chickens, but not geese. The liver has crucial functions in the regulation of energy metabolism during embryogenesis, but its involvement in green light transduction is still unidentified. We aimed to determine the influence of monochromatic green light on Yangzhou goose hatching performance and embryo development. We also investigated the metabolomics and transcriptomic responses of the embryonic liver to green light to determine the underlying molecular mechanisms. Eggs were incubated under either 12 h of monochromatic green light/dark (12 L:12D) cycles or 24 h of darkness (0G:24D). Green light promoted embryonic development and hatching performance, also affected the expression of myogenic regulatory factors associated with muscle development. It also shortened hatching time and elevated plasma levels of growth hormone and insulin-like growth factor-1. Metabolomics and transcriptomic results revealed differentially expressed genes and metabolites with enhanced gluconeogenesis/glycolysis and increased plasma glucose and pyruvate levels under green light. Hence, the growth-promoting effect possibly through regulating energy metabolism in the liver and myogenic regulatory factors in muscle. Our findings provide important and novel insights into the mechanisms underlying the beneficial effects of green light on goose embryos.

ROS downregulate TCA activity to modulate energy metabolism via the HIF/miR-34/ACS-PK pathway for lifespan extension in Helicoverpa armigera

Previous studies have shown that high levels of reactive oxygen species (ROS) and low tricarboxylic acid (TCA) activity in the brain promote pupal diapause, which is characterized by metabolic depression and lifespan extension. However, it is unclear whether ROS are associated with TCA activity. In this study, we demonstrate that ROS downregulate TCA activity and acetyl-CoA and pyruvate levels in the brains of diapause-destined pupae in the moth Helicoverpa armigera, as well as the protein levels of acetyl-CoA synthetase (ACS) and pyruvate kinase (PK), two proteins involved in the biosynthesis of acetyl-CoA and pyruvate, respectively. Interestingly, miR-34, which is highly expressed in the brains of diapause-destined pupae, can respond to ROS signaling. Furthermore, we show that miR-34 can reduce the expression of ACS and PK by directly targeting their mRNAs. Additionally, hypoxia-inducible factor (HIF), a transcription factor, can be activated by ROS and then promotes miR-34 transcription by binding a cis-element in its promoter. Moreover, we observed delayed pupal development after treatment with a ROS activator paraquat and a HIF activator dimethyloxallyl glycine. Taken together, these results suggest that a novel pathway ROS/HIF/miR-34/ACS-PK was found to negatively regulate TCA activity to promote insect diapause for lifespan extension.

514 ATAXIA TELANGIECTASIA MUTATED PROTEIN MODULATES GLUCOSE AND LIPID METABOLISM IN THE HEART

Abstract Background Ataxia Telangiectasia Mutated (ATM) protein kinase is the major sensor of DNA damage response (DDR) and oxidative stress, variously implicated in cellular metabolism. Previous studies on ATM functions in the heart have produced conflicting results. Here we hypothesized that ATM might regulate cardiomyocyte metabolic homeostasis and function. Methods Atm-mutated mice (Atm-/-) and their wild-type littermates (Atm+/+) were used to assess the effects of ATM inactivation on cardiomyocyte hypertrophy, cardiac structure, function, DDR and metabolism under sham conditions or after pressure overload by transverse aortic constriction (TAC). Results ATM inactivation induced cardiomyocyte hypertrophy (FIG.1 A), fetal gene expression re-activation and a specific metabolomic signature in the heart, characterized by significant accumulation of pyruvate, branched chain amino-acids, short-medium acyl-carnitines and metabolites of tricarboxylic acid cycle (FIG.1 C, D),. Importantly, pyruvate was trapped in the cytosol because mitochondrial carriers were suppressed and the enzymes that process pyruvate were dysregulated. As a consequence of pyruvate metabolic block, fatty acids oxidation was inefficient and resulted in the accumulation of acyl-carnitines and insulin resistance. Although these metabolic changes were present constitutively in Atm-/- mice, they were amplified by TAC, which rapidly induced heart failure (FIG.1 B) in Atm-/- mice. ATM inactivation also increased basal and TAC-induced genomic stress in cardiomyocytes, as shown by the levels of p-γ-H2AX, 8-oxodG glycosylase (OGG1/2) and apurinic site nuclease (APE1). Cardiac metabolic changes induced by ATM loss (rise of pyruvate, lactate and succinate levels) were also present in Atm-/- brains, although the basal conditions were different. Conclusions ATM rewires the metabolism of cardiac cells by inducing glycolysis and fatty acids oxidation. Combining metabolomic, DNA damage and cardiac phenotypes, we deduce that ATM stimulates glycolysis to repair DNA lesions and protect the heart against stress-induced dysfunction.