Репозиторий Университета

© 2020 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC SLC2A3 encodes the predominantly neuronal glucose transporter 3 (GLUT3), which facilitates diffusion of glucose across plasma membranes. The human brain depends on a steady glucose supply for ATP generation, which consequently fuels critical biochemical processes, such as axonal transport and neurotransmitter release. Besides its role in the central nervous system, GLUT3 is also expressed in nonneural organs, such as the heart and white blood cells, where it is equally involved in energy metabolism. In cancer cells, GLUT3 overexpression contributes to the Warburg effect by answering the cell's increased glycolytic demands. The SLC2A3 gene locus at chromosome 12p13.31 is unstable and prone to non-allelic homologous recombination events, generating multiple copy number variants (CNVs) of SLC2A3 which account for alterations in SLC2A3 expression. Recent associations of SLC2A3 CNVs with different clinical phenotypes warrant investigation of the potential influence of these structural variants on pathomechanisms of neuropsychiatric, cardiovascular, and immune diseases. In this review, we accumulate and discuss the evidence how SLC2A3 gene dosage may exert diverse protective or detrimental effects depending on the pathological condition. Cellular states which lead to increased energetic demand, such as organ development, proliferation, and cellular degeneration, appear particularly susceptible to alterations in SLC2A3 copy number. We conclude that better understanding of the impact of SLC2A3 variation on disease etiology may potentially provide novel therapeutic approaches specifically targeting this GLUT.

© 2020 Elsevier B.V. The development of cardiovascular diseases (CVDs) is often asymptomatic. Identification of initial indicators of cardiometabolic disruption may assist in its early detection. The objective was to determine the relationships between plasma acylcarnitines (ACs) and cardiometabolic risk factors in adults with and without CVDs. The AC profile in human plasma of healthy controls [non-CVD group, n = 13)] and individuals diagnosed with CVDs (CVD group, n = 34) were compared. A targeted analysis of 29 ACs was performed using flow injection analysis-tandem mass spectrometry. There were significant direct correlations (p < 0.05) between ACs and cardiometabolic risk factors. Comparing the groups after adjustment for covariates, showed that the ACs that were best differentiated (p < 0.05) between the two groups and that presented “good” diagnostic accuracy were carnitine [30.7 (25.5–37.7) vs. 37.7 (32.3–45.0) µM], the short-chain ACs: acetylcarnitine [8.9 (7.4–10.2) vs. 11.9 (9.2–14.4) µM] and isovalerylcarnitine [0.10 (0.06–0.13) vs. 0.13 (0.10–0.16) µM], and the medium-chain ACs: hexanoylcarnitine [0.04 (0.03–0.05) vs. 0.06 (0.05–0.07) µM] and decenoylcarnitine [0.18 (0.12–0.22) vs. 0.22 (0.17–0.32) µM]. This assessment contributes to the identification of the unique metabolic features exhibited in association with cardiometabolic risk in adults diagnosed with CVD. The altered metabolites have the potential to be used as biomarkers for early detection of CVD.

© 2019 Elsevier B.V. Background: Skeletal muscle cells continuously generate reactive oxygen species (ROS). Excessive ROS can affect lipids resulting in lipid peroxidation (LPO). Here we investigated the effects of myotube intracellular calcium-induced signaling eliciting contractions on the LPO induction and the impact of LPO-product 4-hydroxynonenal (4-HNE) on physiology/pathology of myotubes using C2C12 myoblasts. Methods: C2C12 myoblasts were differentiated into myotubes, stimulated with caffeine and analyzed for the induction of LPO and formation of 4-HNE protein adducts. Further effects of 4-HNE on mitochondrial bioenergetics, NADH level, mitochondrial density and expression of mitochondrial metabolism genes were determined. Results: Short and long-term caffeine stimulation of myotubes promoted superoxide production, LPO and formation of 4-HNE protein adducts. Furthermore, low 4-HNE concentrations had no effect on myotube viability and cellular redox homeostasis, while concentrations from 10 μM and above reduced myotube viability and significantly disrupted homeostasis. A time and dose-dependent 4-HNE effect on superoxide production and mitochondrial NADH-autofluorescence was observed. Finally, 4-HNE had strong impact on maximal respiration, spare respiratory capacity, ATP production, coupling efficiency of mitochondria and mitochondrial density. Conclusion: Data presented in this work make evident for the first time that pathological 4-HNE levels elicit damaging effects on skeletal muscle cells while acute exposure to physiological 4-HNE induces transient adaptation. General significance: This work suggests an important role of 4-HNE on the regulation of myotube's mitochondrial metabolism and cellular energy production. It further signifies the importance of skeletal muscle cells hormesis in response to acute stress in order to maintain essential biological functions.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Diet plays an important role in the development of obesity and may contribute to dysregulated iron metabolism (DIM). A cross-sectional survey of 208 adults was conducted in Taipei Medical University Hospital (Taipei, Taiwan). A reduced-rank regression from 31 food groups was used for a dietary pattern analysis. DIM was defined as at least four of the following criteria: serum hepcidin (men >200 ng/mL and women >140 ng/mL), hyperferritinemia (serum ferritin of >300 ng/mL in men and >200 ng/mL in women), central obesity, non-alcoholic fatty liver disease, and two or more abnormal metabolic profiles. Compared to non-DIM patients, DIM patients were associated with an altered body composition and had a 4.52-fold (95% confidence interval (CI): (1.95–10.49); p < 0.001) greater risk of metabolic syndrome (MetS) after adjusting for covariates. A DIM-associated dietary pattern (high intake of deep-fried food, processed meats, chicken, pork, eating out, coffee, and animal fat/skin but low intake of steamed/boiled/raw foods and dairy products) independently predicted central obesity (odds ratio (OR): 1.57; 95% CI: 1.05–2.34; p < 0.05) and MetS (OR: 1.89; 95% CI: 1.07–3.35; p < 0.05). Individuals with the highest DIM pattern scores (tertile 3) had a higher visceral fat mass (%) (β = 0.232; 95% CI: 0.011–0.453; p < 0.05) but lower skeletal muscle mass (%) (β = −1.208; 95% CI: −2.177–−0.239; p < 0.05) compared to those with the lowest DIM pattern scores (tertile 1). In conclusion, a high score for the identified DIM-associated dietary pattern was associated with an unhealthier body composition and a higher risk of MetS.

© 2018 Sychev et al. Cytochrome (CYP) 450 isoenzymes are the basic enzymes involved in Phase I biotransformation. The most important role in biotransformation belongs to CYP3A4, CYP2D6, CYP2C9, CYP2C19 and CYP1A2. Inhibition and induction of CYP isoenzymes caused by drugs are important and clinically relevant pharmacokinetic mechanisms of drug interaction. Investigation of the activity of CYP isoenzymes by using phenotyping methods (such as the determination of the concentration of specific substrates and metabolites in biological fluids) during drug administration provides the prediction of negative side effects caused by drug interaction. In clinical practice, the process of phenotyping of CYP isoenzymes and some endogenous substrates in the ratio of cortisol to 6β-hydroxycortisol in urine for the evaluation of CYP3A4 activity has been deemed to be a quite promising, safe and minimally invasive method for patients nowadays.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: Prolongation of the QT interval in patients with coronary heart disease (CAD) is a risk factor of polymorphic ventricular tachycardia (PVT) and as consequence, the sudden death. Drug-drug interactions (DDI) on metabolic rate involving cytochrome P-450 (CYP) is the one of the major cause of Long QT Syndrome (LQTS). The aim of the present study was to improve the safety of combined pharmacotherapy when using drugs that affect the QT interval. Method and Results: Medication occurrence of potential dangerous combination of medicines that are affected on QT interval duration in patients with CAD are researched (outpatient medical records (patient history) analysis). Clinical relevance of DDI, which are associated with changes in CYP enzyme activity, categorized by drugs.com Medication Guide. Finding potential dangerous combination of medicines that are affected on QT interval duration were administered to patients with CAD in 3.6% cases in outpatient clinical practice. The most often prescribed combination of drugs is amiodarone and torasemide (13.3% evidence of all concomitant administration that are leading to QT prolongation). The potential mechanism of Amiodarone and Torasemide interaction on metabolic rate that are leading to QT prolongation are competitive substrates CYP 2C8 and a result of inhibited CYP 2C9 by amiodarone. Conclusion: Ability to predict the prolongation of the QT interval caused by DDI on metabolic rate make possible to improve the safety concomitant administration to patients with CAD.

© 2018 S. Karger AG.All right reserved. Objective: to estimate the state and the rate of bone metabolism in women with chronic kidney disease (CKD) 1-3 stages during pregnancy. Materialsandmethods:observational cross-sectional and prospective study included 137 pregnant women. CKD 1-3 stage had 85 of them: 64 with CKD 1-2 stage, 21 with CKD 3 stage. Median age 29 years, second and third trimester (42 and 37, respectively). The comparison group consisted of 52 pregnant women with of the same age and gestational age without CKD. Dynamic examination was carried out in 18 cases with CKD 1-3 stage. Ionized, total calcium and inorganic phosphorus, 25-OH vitamin D, parathyroid hormone (PTH), the activity of total alkaline phosphatase (ALP), osteocalcin (OC), N-terminal propeptid of type 1 procollagen (P1NP) and β-isomer of C-terminal telopeptide of type I collagen (β-CTX) were determined. Results: serum calcium, phosphorus and PTH levels in all the examined pregnant women were within their normal range. In pregnant with CKD 3 stage, a deficiency of vitamin D was more significant (р0.02) compared to pregnant women without CKD and pregnant with CKD 1-2 stage. The levels OC and P1NP and β-CTX in pregnant with CKD 3 stage were higher than in the control group and pregnant women with CKD 1-2 stage. It was also higher in pregnant women with CKD 1-3 stages in the third trimester in comparison with the second one, although remained within the limits of reference values. Significant direct correlations were found between serum concentrations of P1NP and OC (r=0.575, р0.001), P1NP and ALP (r=0.415, р=0.001), OC and ALP (r=0.276, р=0, 02) and vitamin D and PTH (r=0.235, р=0.04). A significant inverse correlation was found between the blood levels of vitamin D and P1NP (r=-0.344, р=0.002). Conclusions: the peculiarities of bone metabolism in pregnant with CKD of 3 stage are manifested by the vitamin D deficiency and the acceleration of bone formation and resorption to a greater extent in the third trimester.

© COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only. The development of express method for assessing the state of skin graft by the spectroscopic properties of tissue components involved in the healing of the affected skin or healing of skin grafts was carried out in present work. The proposed method for assessing the state of the skin by the spectroscopic properties of tissue components (using photosensitizers, fluorescent dyes (methylene blue and IcG) and nanophotosensitizers aluminum phthalocyanine nanoparticles (NP-AlPc) applied locally) will evaluate the physiological condition of the skin and assess the degree and rate of engraftment or rejection while also controlling several biochemical and physiological parameters in the entire graft, or the whole area of the skin lesions. Such parameters include the oxygenation of hemoglobin in the tissue microvasculature; the blood supply level; blood flow and lymph flow; assessment of intracellular metabolism; assessment of the cellular respiration type (aerobic/anaerobic).To assess the extent of inflammation the spectrally sensitive to biological environment nanoparticles of aluminum phthalocyanine (NP-AlPc) were also used.

© 2018 Bentham Science Publishers. Background: Nitroproston is a novel prostaglandin-based compound modified by NO-donating groups with potential application in obstructive respiratory diseases such as asthma and obstructive bronchitis. Nitroproston has been extensively studied using various pharmacological models. Its biological stability is still uncertain. Objective: The aim of the present study was to evaluate Nitroproston stability in vitro, as well as to identify and characterize its major biodegradation products. Methods: The principal biodegradation products of Nitroproston were identified in vitro using liquid chromatography/ion trap – time-of-flight mass-spectrometry. The postulated structure of metabolites was confirmed using authentic reference standards. Rat, rabbit and human plasma and human whole blood samples were used for comparative in vitro degradation study. Nitroproston and its biodegradation products in biological samples were measured by liquid chromatography/triple –stage quadrupole mass spectrometry. Results: Nitroproston is rapidly hydrolyzed in rat plasma to generate glycerol-1,3-dinitrate and prostaglandin E2 . The latter can undergo conversion to cyclopentenone prostaglandins A2 and B2 . Thereby less than 5% of the parent compound was observed in rat plasma at the first moment of incubation. A similar pattern was observed for rabbit plasma where half-life (T1/2) of Nitroproston was about 2.0 minutes. Nitroproston biodegradation rate for human plasma was the slowest (T1/2 = 2.1 h) among tested species, occurred more rapidly in whole blood (T1/2 = 14.8 min). Conclusion: It was found that Nitroproston is rapidly hydrolyzed in rodent compared to human plasma incubations. Whereas Nitroproston is relatively stable in human plasma an enhanced hydrolytic activity was observed in whole human blood incubations. Extensive metabolism of Nitroproston in human whole blood was mainly associated with red blood cells. The observed interspecies variability highlights the need of suitable animal model selection for Nitroproston follow-up PK/PD studies.

© 2018, © 2018 Informa UK Limited, trading as Taylor  &  Francis Group. A growing body of evidence has hinted at the involvement of the largest gene of the circadian clock family, NPAS2, in the regulatory mechanisms underlying the link between metabolic diseases and circadian rhythm disruption. We tested whether one of single-nucleotide polymorphisms in NPAS2 (rs4851377) is associated with obesity and alternations of sleep times in 126 male rotational shift workers (bus drivers). We confirmed positive association of Body Mass Index (BMI) with the difference between free and working days in sleep times, but this difference was smaller in the homozygotes for the minor allele. Moreover, BMI above 30 (obesity) was revealed in the majority of these homozygotes and in the minority of homozygotes for the major allele (11 of 21 or 52.4% and 3 of 40 or 7.5%, respectively). Further studies are required to replicate these results and to elucidate the mechanisms linking NPAS2ʹpolymorphism in with obesity in shift workers.

Objectives: Central (hypogonadotropic) hypogonadism in women could be a cause of persistent amenorrhea and hypoestrogenemia as observed in postmenopause. This study aimed to compare the clinical, hormonal and biochemical features in women with non-physiological (central hypogonadism) and physiological (postmenopause) hypoestrogenemia.

Methods: A total of 161 young women, median age 24.9 years (interquartile range (IQR) 21.2; 30.5) with central hypogonadism (with isolated hypogonadotropic hypogonadism, n = 76, and with hypopituitarism, n = 85), 53 healthy young women, median age 23.9 years (IQR 23.1; 28.0) and 50 healthy postmenopausal women, median age 56.0 years (IQR 53.1; 58.5), were examined. Psychoemotional, neurovegetative and urogenital symptoms, sex steroid levels, parameters of lipid and mineral metabolism were evaluated.

Results: In young women with central hypogonadism, the frequencies of psychoemotional, neurovegetative and urogenital complaints differed significantly from those in healthy young women and were similar to those in postmenopausal women. Concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, parameters of lipid and mineral metabolism as well as quality of life in women with central hypogonadism were not typical of healthy young women but were similar to those of postmenopausal women of middle/old age.

Conclusions: Despite the young age of women with central hypogonadism, clinical, hormonal and biochemical abnormalities were similar in many aspects to those in postmenopausal women at middle/old age. These revealed features could be considered as signs of premature aging in young amenorrheic women with low gonadotropin levels.

Objectives: Central (hypogonadotropic) hypogonadism in women could be a cause of persistent amenorrhea and hypoestrogenemia as observed in postmenopause. This study aimed to compare the clinical, hormonal and biochemical features in women with non-physiological (central hypogonadism) and physiological (postmenopause) hypoestrogenemia.

Methods: A total of 161 young women, median age 24.9 years (interquartile range (IQR) 21.2; 30.5) with central hypogonadism (with isolated hypogonadotropic hypogonadism, n = 76, and with hypopituitarism, n = 85), 53 healthy young women, median age 23.9 years (IQR 23.1; 28.0) and 50 healthy postmenopausal women, median age 56.0 years (IQR 53.1; 58.5), were examined. Psychoemotional, neurovegetative and urogenital symptoms, sex steroid levels, parameters of lipid and mineral metabolism were evaluated.

Results: In young women with central hypogonadism, the frequencies of psychoemotional, neurovegetative and urogenital complaints differed significantly from those in healthy young women and were similar to those in postmenopausal women. Concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, parameters of lipid and mineral metabolism as well as quality of life in women with central hypogonadism were not typical of healthy young women but were similar to those of postmenopausal women of middle/old age.

Conclusions: Despite the young age of women with central hypogonadism, clinical, hormonal and biochemical abnormalities were similar in many aspects to those in postmenopausal women at middle/old age. These revealed features could be considered as signs of premature aging in young amenorrheic women with low gonadotropin levels.